Feeding rats a semiliquid ethanol diet for a period of four weeks prod
uced a hepatic accumulation of the methylating agent N-5-methyltetrahy
drofolate ((NCH3THF)-C-5). When the ethanol-containing diet was supple
mented with 0.5% betaine, an agent known to promote the generation of
methionine and S-adenosylmethionine (SAM) in ethanol-fed animals, the
accumulation of (NCH3THF)-C-5 was prevented. One index that the methyl
folate trap exists is the hepatic accumulation of (NCH3THF)-C-5, and
a second index is that the (NCH3THF)-C-5 accumulation can be relieved
by methionine administration. Since ethanol is shown to produce (NCH3T
HF)-C-5 accumulation in this study, and since betaine (a generator of
methionine and SAM) acts to eliminate this accumulation, it is suggest
ive that ethanol can contribute to the impairing hepatic condition ref
erred to as the ''methyl folate trap.''