Epigenetics and nutrition: B-vitamin deprivation and its impact on brain amyloid

Epigenetics is becoming the epicentre of modern medicine because it is beginning to clarify the relationship between genetic background, environment, aging, and disease. SAM-dependent DNA methylation at the 5-position of cytosine within CpG dinucleotides represents an important mechanism for epigenetic control of gene expression and maintenance of genome integrity. Hence, methyl deficiency leads to disturbances in gene expression. B vitamins (B12, B6, and folate) have a pivotal role in reducing homocysteine accumulation by remethylation to form methionine and by transsulfuration to form glutathione (GSH). B vitamins have therefore a central function in SAM synthesis, in gene expression, and in the synthesis of one of the major antioxidant molecules. The physiological causes of AD onset are not yet well understood, but it has been shown that changes in DNA methylation due to vitamin deficiency contributes to the basic mechanisms responsible for AD onset. Accordingly, restoration of gene methylation pattern could be a target for preventing AD or arresting the progression of disease. A methyl donor such as SAM can repair the DNA methylation pattern and thereby restore normal biological functions in AD mice. Recent studies indicate that B vitamin deprivation and SAM supplementation, which modify the SAM cycle, can influence amyloidogenesis in mice, probably via SAM-dependent methylation reactions. SAM supplementation has been shown to reduce beta amyloid in mice brain.