Effect of high levels of dietary folic acid on folate metabolism in vitamin B12 deficiency

Abstract The effect of administering high levels of folic acid to vitamin B 12 -deficient animals was studied. In B 12 deficiency histidine oxidation is decreased. This is the result of both decreased liver folate levels and increases in the proportion of methyltetrahydrofolates. The purpose of this study was to determine if the addition of very high levels of folic acid to B 12 -deficient diets could increase liver folates and thereby restore histidine oxidation. Rats were fed a soy protein B 12 -deficient diet containing 10% pectin which has been shown previously to accelerate B 12 depletion. When this diet was supplemented with B 12 and folic acid, histidine oxidation was 5.4% in 2 h and the livers contained 3.49 μg of folate/g. In the absence of B 12 , the histidine oxidation rate was 0.34% and the liver folate level was 1.33 μg/g. When 200 mg/kg of folic acid was added to the B 12 -deficient diet there was no increase in histidine oxidation (0.35%) but the liver folates were increased to 3.68 μg which is about the same as that with B 12 supplementation. The percentage tetrahydrofolate of the total liver folates was the same with and without a high level of dietary folic acid. Thus there was an increase in the absolute level of tetrahydrofolate without any increase in folate function as measured by histidine oxidation. Red cell folate levels were the same with and without B 12 , which is in contrast to the markedly lower liver folate levels in B 12 deficiency. These data suggest a difference between B 12 regulation of folate metabolism in the liver and in the bone marrow.