Clearance in plasma of pteroylglutamic acid (PGA) was determined in human adults and newborns. The doses of PGA given to adults were 7.5 and 15 figjkg and those given to newborns were 15 and 30 ,«g/kg of body weight, respectively. Microbiological assays using Lactobacillus casei determined the total folate in serum as well as the amount of unchanged PGA following intravenous administration of PGA. Excretion of folate was determined in adults and newborns receiving 40 fig PGA/kg intramuscularly.Clearance of folic acid in plasma was found to be much more rapid in newborns than in adults (figs. 1 and 2). Less folate was excreted in the urine by the newborns (table I) which indicated that rapid clearance of folic acid in plasma in the newborns was due to rapid tissue uptake of folate. SpeculationThe rapid tissue uptake of PGA in newborns indicates the markedly increased demand for folic acid in the neonatal period and during the period of early infancy, when there is a rapid rate of cell replication and growth. This finding explains the rapid fall of serum [20] and blood folate levels [16] in the first few months of life when the increased demand for folate is not met by the dietary folate. Further studies are needed to determine folate stores in newborns, the dietary intake of folate by newborns, and the folate requirement of newborns and infants. Introductionwas any block in the utilization of folic acid in the newborn period when the folate level in serum was very Reported studies [21] have shown that the peak folate high [5,9,16,20]. level in serum after an intramuscular dose of PGA was lower in newborns than in adults, suggesting a more rapid clearance of folic acid in the newborn infant. TheMaterials and Methods experiments reported in this present paper were designed to study the clearance of folic acid in plasma in Subjects were 12 normal adult volunteers (hospital the newborn and to see whether the rapid clearance personnel) and 9 normal full-term newborns (6-12 was due to rapid tissue uptake or increased loss in the days old) [25]. The technique of blood collection and urine. They were also designed to see whether there the source of folic acid for standard and test doses have
ExtractFolic acid (PGA) absorption (40 ,«g/kg of body weight) was studied in normal newborns and adults using Lactobacillus casei and Streptococcus faecalis microbiological assays for folate determination. The PGA was given orally or intramuscularly to the subjects after either saturating their tissues with folate or without prior saturation of their tissues. Without prior saturation of the tissues the folic acid absorption curves in newborns were much lower than those found in adults (figs. 1 and 2). Saturation of the tissues of the newborns with folic acid, prior to administration of the oral test dose, raised the absorption curves of the folic acid, but these were still lower than those seen in adults (fig: 5). The folate curve of the newborns after an intramuscular test dose of PGA was also lower than that observed in adults (fig. 3); however, after saturating the tissues of the newborns with folic acid, the folate curve became comparable to that of the unsaturated adults ( fig. 4).After the oral test dose, newborns excreted a much smaller percentage of the administered dose in their urine than did the adults (table II). When the tissues in newborns were saturated with folic acid, however, the excretion of folate in the urine became comparable to that of unsaturated adults (table II) These data indicate that: 1) plasma clearance of folate in newborns is more rapid than that in adults and that large saturating doses of folic acid are needed to reduce this clearance rate; and 2) the folate absorption curve in the newborn is lower than in the adult. With the criteria set for adults, this could be interpreted as evidence of impaired folate absorption in newborns. The proper interpretation of the data indicates, however, that folate absorption by newborns is slower than seen in adults and that the net absorption is comparable to that of adults. SpeculationIn newborns, the absorption curve for orally administered folate is lower than in adults. Our study indicates that this is due to the slower absorption of folates and more rapid tissue uptake of folates by newborns. Further studies should be carried out to investigate the absorption of folate conjugates which are the main forms of folate found in food, to determine how much of the folate in food is available to newborns and small infants, and to evaluate the need for supplementary folate in small infants. SHOJANIA and HORNADY 413
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