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

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. Herein, 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 drugs, 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 the reconstitution potential in transplantation settings and increase radiation-induced mortality. We conclude that excessive folic acid supplementation can metabolically mimic dietary folate insufficiency, leading to similar functional impairment of hematopoiesis.

A Review on the Serum Electrolytes and Trace Elements Role in the Pathophysiology of COVID-19

“…It has important roles in immune functions including immunoglobulin synthesis and immunoglobulin M (IgM) lymphocyte binding [51] ND Folic acid Synthesis of purines and thymidylate that they are necessary for mitochondrial producing of ATP need folic acid [65] Folic acid impairs the viral life cycle by creating hydrogen binds with 3CL hydrolase. In severe patients, the level of folic acid is lower [52,64]…”

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

“…Module 7 (Fig. 6a,c,d) represents another set of metabolic activities including folate and serine metabolism as well as the nucleotide biosynthesis pathway typically associated with the progenitor populations [25][26][27] . In addition to the yolk sac macrophages, this module is also enriched in some tissue residing dendritic cells and pDCs (but not in migDCs).…”

Balance your folate or the yin and yang of folate in hematopoiesis

“…1 Although the study was limited by small sample size, the authors noted no significant differences in all important post-HSCT clinical outcomes, including survival, between tMDS and de novo MDS patients, even when prior chemoradiotherapy was considered in multivariable models. This analysis therefore suggests that allogeneic transplantation for tMDS should be performed whenever it would be considered in the de novo MDS setting.…”

“…1 Given that there are substantial fractions of the world population at risk for either excessive (via fortified diets) or very low folate intake, this study might contribute to novel public policy recommendations on the level of folate intake, specifically in the context of fortified diets.…”

“…The toxicity of folic acid has, up to now, been universally regarded as being very low, as folate is a water-soluble vitamin and thus an excess will be likely removed from the body through urine, as in the case of vitamin C. Henry et al have now addressed, in an elegant set of well designed experiments, the extent to which distinct levels of dietary folate influence B cell development and hematopoiesis, via transplantation experiments in particular. 1 To this end, they simply fed mice diets deficient in folate or diets that contained high levels of folate for up to 12 months. The diet high in folate resulted in folate serum levels that are within the range which are likewise achieved with fortified diets in human serum.…”