Folate Deficiency Associated with Gene Modulation

iStock-629430458.jpgFolate deficiency has been associated with the onset of varied metabolic abnormalities, “including insulin resistance, by altering epigenetic processes on key regulatory genes,” such as the calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2). CAMKK2 is part of the calcium-triggered signaling cascade, and influences obesity and glucose metabolism. 

This study looked at subjects with a total folate intake lower than 300 μg/d, more “fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment–insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1, and compared [these levels] to those consuming ≥ 300 μg/d [of folate].”  They determined that “folate deficiency was related to lower CAMKK2 methylation.

In this study, the methylation of CAMKK2 was “negatively correlated with the Homeostatic model assessment (HOMA-IR),” a method used to assess β-cell function and insulin resistance (IR) from basal (fasting) glucose and insulin or C-peptide concentrations.[1]  Furthermore, they observed that CAMKK2 expression directly correlated with HOMA-IR values, and that folate deficiency was related to lower CAMKK2 methylation.  

In conclusion, this summary proposed “associations between low folate intakes, lower CAMKK2 gene methylation, and insulin resistance in obese individuals.” 


Omar Ramos-Lopez,Mirian Samblas,Fermin I. Milagro,M. Angeles Zulet,Maria L. Mansego,Jose I. Riezu-Boj,J. Alfredo Martinez.  Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects.  Nutrition Research. February 2018 50: 53-62. 



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