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Cumulative Excess Urinary Excretion of Folate in Rats after Repeated Ethanol Treatment^1,2,

Department of Pharmacology, Section of Toxicology, and Department of Biometry, Louisiana State University Medical Center, Shreveport, LA 71130

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 administation 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.

KEY WORDS: • alcoholism • folate deficiency • ethanol • nutrition • urinary folate • excretion

¹ Supported in part by National Institutes of Health Grant AA05308 and by a research grant from the Distilled Spirits Council of the United States, Inc.

² Presented in preliminary form at the annual meeting of the Federation of American Societies for Experimental Biology, St. Louis, MO, April. (1984) Fed. Proc. 43, 494.

Manuscript received 27 August 1985. Revision accepted 12 February 1986.