The effect of diet and alcohol on the development of folate deficiency in the rat.

Studies of the rate of depletion of serum and tissue methylated and non-methylated folates were carried our in rats maintained for long periods on either a folate deficient (sucrose-water/sulphathiazole) diet or a deficient diet plus high alcohol intake. By means of implantation of a feeding gastrostomy tube, it was possible to sustain constant blood ethanol levels of between 50 and 300 mg/dl for 3-4 weeks with relatively normal calorie intake and without death of the animal. Using this animal model, which closely resembles severe alcoholism in man, a very rapid depression in serum 5-methyl tetrahydrofolate was observed similar to that reported in alcoholic man. At the same time, release of folates from liver stores was umimpaired by alcohol ingestion. Liver folate store depletion rates were identical for alcoholic and folate starved animals. The explanation for the sudden alcohol suppression of serum folate levels must, therefore, be sought at a point in the internal metabolic sequences of folate other than the delivery of folate stores to plasma.