The relationship of ethanol feeding to the methyl folate trap

Feeding rats a semiliquid ethanol diet for a period of four weeks produced a hepatic accumulation of the methylating agent N5-methyltetrahydrofolate (N5CH3THF). When the ethanol-containing diet was supplemented with 0.5% betaine, an agent known to promote the generation of methionine and S-adenosylmethionine (SAM) in ethanol-fed animals, the accumulation of N5CH3THF was prevented. One index that the methyl folate trap exists is the hepatic accumulation of N5CH3THF, and a second index is that the N5CH3THF accumulation can be relieved by methionine administration. Since ethanol is shown to produce N5CH3THF accumulation in this study, and since betaine (a generator of methionine and SAM) acts to eliminate this accumulation, it is suggestive that ethanol can contribute to the impairing hepatic condition referred to as the "methyl folate trap."