The incidence of neural tube defects was studied in mouse embryos from dams fed an amino acid-based diet containing 45, 91, 136, 181, 227 or 453 nmol folic acid/kg diet (Experiment 1) or 227, 453, 566, 680, 906, 1132, 1698 or 2266 nmol folic acid/kg diet (Experiment 2). Reproductive tracts were examined 12 d postcoitum and gross and microscopic examination of all embryos was performed. A single implantation was found at levels less than or equal to 181 nmol folic acid/kg diet. With one exception, bred mice fed 227 or 453 nmol folic acid/kg diet in Experiment 1 had 100% resorptions. In Experiment 2, 100% of implantations in mice fed 227 nmol folic acid/kg diet and approximately 75% of implantations in mice fed 453 or 566 nmol folic acid/kg diet resorbed. The 906 nmol folic acid/kg diet was sufficient for successful pregnancy. Mice fed 227 nmol folic acid/kg diet in Experiment 2 weighed approximately 80% of mice fed higher levels of folic acid. Inadequate dietary folic acid resulted in fewer and smaller embryos (which developed normally). These results suggest that folate deficiency alone is insufficient to produce neural tube defects in Swiss-Webster mice. Because individual micronutrients (e.g., folate) can be omitted from the amino acid-based diet, the specific role of folic acid in neurulation can now be studied systematically.

To clarify relationships between dietary folic acid intake, blood levels and body stores of folate, rats were fed an amino acid-based diet supplemented with 0, 0.125, 0.5, 1, 2 or 4 mg folic acid/kg diet for 25 d. Folate concentrations of carcass, liver, gastrointestinal (GI) tract, kidney, spleen, testes, heart and lung from rats fed the folate-free diet were 0.06 +/- 0.01, 0.73 +/- 0.08, 0.05 +/- 0.01, 0.39 +/- 0.01, 0.05 +/- 0.01, 0.17 +/- 0.01, 0.02 +/- 0.01 and 0.02 +/- 0.01 micrograms/g, respectively. Serum and erythrocyte concentrations and total body stores were 0.88 +/- 0.16 ng/mL, 0.30 +/- 0.01 micrograms/mL and 13.9 +/- 0.7 micrograms, respectively. Body folate distribution was carcass, 55.6 +/- 1.4%; liver, 26.0 +/- 1.9%; erythrocytes, 7.7 +/- 0.4%; kidney, 4.8 +/- 0.2%; GI tract, 3.0 +/- 0.2%; and testes, 2.5 +/- 0.2%. Carcass content dropped to 38% whereas liver content increased to 44% in rats fed the highest dietary level. Tissue concentrations were correlated with one another and with dietary folate levels. Under these experimental conditions total body folate could be predicted from serum folate, but the general applicability of this relationship requires further study.

Folate bioavailability of beef liver, lima beans, peas, spinach, mushrooms, collards, orange juice and wheat germ was estimated with a protocol of folate depletion-repletion using growth and liver, serum and erythrocyte folate of weanling male rats. Diets with 125, 250 and 375 micrograms folic acid/kg were standards. Individual foods were incorporated into a folate-free amino acid-based diet alone (250 micrograms folate/kg diet from food) or mixed with folic acid (125 micrograms folate from food + 125 micrograms folic acid) to evaluate folate bioavailability and effects of food matrix. Beef liver and orange juice folates were as available as folic acid, whereas those of wheat germ were less bioavailable. Folates of peas and spinach were also less available than folic acid using liver and serum folate concentrations and total liver folate as response criteria, but they were not lower when based on growth and erythrocyte folate concentrations. Lima bean, mushroom and collard folates were as available as folic acid using four of five response criteria. Folate bioavailability of all foods generally exceeded 70%. All response criteria gave approximately equivalent results, indicating that growth and tissue folate levels are appropriate criteria. No food matrix effects were observed for any food except lima beans. Foods rich in polyglutamyl folates were less bioavailable than those of foods rich in short-chain folates.

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