Cumulative excess urinary excretion of folate in rats after repeated ethanol treatment

The folate deficiency that is produced by chronic alcohol ingestion results from poor dietary intake and from effects of ethanol on folate metabolism and absorption. Previous studies in fasted rats showed that singular treatment with ethanol produces an increase in urinary folate levels, in amounts that account for a subsequent decrease in plasma folate levels. The effects of subacute administration of ethanol on urinary folate excretion were studied in fed and fasted rats treating for 1, 2, 3 or 4 d either with ethanol orally in four doses of 1 g/kg each at hourly intervals or with glucose in isocaloric doses. Urine was collected at timed intervals up to 12 h after each daily dose. Rats were fed daily except for the evening prior to the final treatment day. Ethanol treatment produced an increase in urinary folate excretion in fed and in fasted rats, although the effect in fed rats was less marked. The increased excretion was similar on each final day, whether rats were treated for 1, 2, 3 or 4 d, indicating that there was no adaptation to the loss of folate during this subacute treatment. The excess urinary folate excretion accumulated so that the longer the rats were exposed to ethanol, the greater the urinary loss. These results suggest that when animals are chronically treated with ethanol, urinary folate loss could contribute to the development of folate deficiency.