DNA methylation and subclinical vitamin deficiency of folate, pyridoxal-phosphate and vitamin B12 in chronic alcoholics

Alcohol abuse is known to adversely affect folate, vitamin B12 and pyridoxal-phosphate metabolism, which are required for de novo synthesis of methionine. Methionine is the precursor of S-adenosylmethionine, the principal methylating agent in the organism, including DNA. The objective of this study was to measure DNA methylation in peripheral lymphocytes and the circulating concentrations of these three vitamins in chronic alcoholics. DNA methylation was assessed by measuring DNA methyl accepting capacity in the presence of Sss1 methylase. Serum pyridoxal-phosphate and red blood cell folate concentrations were significantly depressed in alcoholics (P < 0.0001 and P = 0.02, respectively). DNA from patients who consumed 3.0 g/ethanol/kg/day or more, incorporated significantly more (H-3) methyl groups, which reflects a lower state of intrinsic methylation (P = 0.01). DNA hypomethylation was also more pronounced in malnourished alcoholics (P = 0.03). We conclude that heavy ethanol consumption is associated with folate and vitamin B6 depletion, which may interfere with DNA methylation status by impairing de novo methionine synthesis.