Repletion of Folate-Depleted Rats with an Amino Acid—Based Diet Supplemented with Folic Acid

Abstract

Folate depletion and repletion protocols are not well standardized. Weanling rats were moderately depleted of folate in 28 d with a folate-free purified diet based on 17% amino acids as the nitrogen source. They were then folate repleted for 23 d with the amino acid diet supplemented with either 125, 250, 500, 1000 or 2000 micrograms folic acid/kg. Hematology, growth and tissue folate levels were measured in subsets of the rats when they were 24 (baseline), 52 (depleted) and 75 d old (repleted). The same measurements were made in control rats that had been fed 2 mg folic acid/kg of the amino acid diet for the same period of time. Our findings show that with repletion, growth of previously depleted rats is in direct proportion with the level of supplementation up to 1000 micrograms folic acid/kg diet. Serum folate levels of repleted rats also increased in proportion to supplementation between 500 to 2000 micrograms/kg diet, and liver folate levels increased proportionally with the level of supplement within the range of 125 to 2000 micrograms/kg diet. The 2000 micrograms/kg supplement was sufficient to restore liver folate levels equivalent to that of controls, but body weight and serum folate levels failed to catch up with that of controls in the 23-d repletion period. There was a nonlinear relationship between serum and liver folate levels: serum folate remained constant at about 6 micrograms/l as liver folate increased to about 7 micrograms/g, then serum folate diverged by increasing to 120 micrograms/l with only minor increases in liver folate.(ABSTRACT TRUNCATED AT 250 WORDS)