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Folate requirement and metabolism in nonpregnant women.

Folate metabolism and requirements were studied in 10 adult nonpregnant women maintained for 92 d in a metabolic unit. After a folate depletion period of 28 d, the subjects received increasing supplements of folate from food items or as pteroylmonoglutamic acid (PGA). Plasma folate levels fell 60% during the depletion period and continued to fall until 200 micrograms/d of naturally occurring food folates were provided. Supplements of 300 micrograms/d of naturally occurring folates produced a small rise in plasma folate levels although erythrocyte folate levels continued to fall. Lymphocyte deoxyuridine suppression, neutrophil hypersegmentation, and other measurements related to folate metabolism were performed. When compared with PGA, dietary folates appeared to be no more than 50% available. A daily intake of 200-250 micrograms of dietary folates appears to meet the folate requirements of nonpregnant adult women whereas an intake of 300 micrograms/d provides an allowance for storage.

Adult↗

Experimental maternal and neonatal folate status relationships in nonhuman primates.

The influence of maternal dietary folic acid intake on folate status was studied in Cebus albifrons monkeys by feeding 10 or 250 micrograms/100 kcal dietary folic acid during pregnancy and 4 wk postpartum. Maternal, infant, and nonpregnant hematologic indices; blood and liver folate concentrations; and urinary formiminoglutamic acid excretion all varied with dietary folate intake and pregnancy status as did milk folate concentration in lactating dams. Maternal folate status, determined by plasma, red blood cell, and milk folate concentrations, as well as urinary formiminoglutamic acid excretion, all were correlated significantly with liver folate concentrations in neonates (r = 0.740, r = 0.919, r = 0.936, and r = -0.851, respectively). Results in these primates showed that neonatal folate status was related significantly to the dietary folate intake and folate status of the mother during pregnancy and lactation.

Animals↗

Folate deficiency in rats fed amino acid diets.

Growth rate, hematological changes, serum, erythrocyte and liver folate levels, and urinary excretion of formiminoglutamic acid (FIGLU) were measured in rats fed p-aminobenzoic acid (PABA)-free, sulfonamide-supplemented purified amino acid diets with and without folic acid and fiber, individually and in combination. Fiber had no effect on growth but was necessary to prevent mortality in the absence of folic acid. Folic acid did not affect growth during the first 40 days, but after this period rats failed to gain weight in the absence of folic acid. Although blood hematocrit was lower when the diet was devoid of fiber and folic acid and leucocyte counts were lower when the diets were devoid of folic acid, the hematological values remained within normal physiological limits for healthy rats of comparable age. FIGLU excretion was increased and serum, erythrocyte and liver folate levels were depressed when rats were fed folic acid-free diets for 28 days. Neutrophil hypersegmentation was clearly evident after 28 days of feeding the folic acid-free diets. The use of an amino acid diet without PABA but containing 5% fiber and 1% succinylsulfathiazole is a useful system to study chronic folic acid deficiency in the rat.

Amino Acids↗

Serum vitamin B12 levels in the aged.

In an attempt to throw light on the question of age-related variations in the normal blood content of cobalamin and on the frequency of deficiencies of antimegaloblastic nutriments in the elderly, 273 geriatric patients have been investigated. Low serum vitamin B12 values were found in one third of these patients, due to latent pernicious anaemia in five and malabsorption in seven cases, and probably caused by nutritional deficiency of folate or cobalamin in 78 cases. In that part of the series with apparently normal vitamin B12 levels, the mean value (379+/-14 pg/ml) was lower than the mean (456+/-20 pg/ml) for a younger control group. However, this cannot be taken as a sign of a physiological lowering of the cobalamin values with age, as nutritional deficiencies could not be ruled out in this part of the series. It is concluded that serum vitamin B12 assays should be performed rather liberally in the aged. Patients with nutritional deficiency of cobalamin or folate should be treated, even if frank megaloblastic anaemia is not present.

Age Factors↗

The effects of chronic drug administration on hepatic enzyme induction and folate metabolism.

1 Patients on prolonged treatment with anticonvulsant and phenothiazine drugs exhibited lower than normal concentrations of folate in serum and erythrocytes, and showed increased urinary FIGLU excretion after histidine loading; urinary excretion of D-glucaric acid was also increased suggesting induction of the hepatic microsomal enzymes. 2 Folate deficiency by enzyme-inducing drugs was seen to be determined more by the duration of therapy than by the nature of the drugs. Excretion of FIGLU was increased by 70% by 2-5 years of treatment with anticonvulsant, phenothiazine or tricyclic drugs, and by 200% after 6 or more years. 3 Hepatic microsomal enzyme induction, as measured by D-glucaric acid excretion, was greatest after 2-5 years treatment. 4 It is suggested that the increased requirements for folate, resulting from microsomal enzyme induction, lead to folate deficiency and this subsequently limits enzyme induction, leading to adverse drug side-affects. 5 The dietary folate of hospitalized patients would seem to be generally inadequate for patients on long term treatment with enzyme-inducing drugs.

Adult↗