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Biomedical subjects

E E Ziegler

Publications and source records attributed to E E Ziegler.

At least 19 recordsLinked to original sources

What is the safe protein-energy ratio for infant formulas?

Infants eat primarily to satisfy energy needs and the safe amount of protein in infant formulas (ie, the amount adequate for nearly all infants) is therefore expressed as the protein-energy ratio. We studied male infants aged 8-112 d fed milk-based formulas. One group (experimental group) was fed formulas that provided protein-energy ratios of 3.73 g/MJ (1.56 g/100 kcal) from 8 to 27 d of age, gradually decreasing to 2.99 g/MJ (1.25 g/100 kcal) from 84 to 111 d of age. Growth rates and serum albumin and urea nitrogen of these infants were compared with those of a concurrently studied control group and a previously studied large reference group. Gains in weight and concentrations of serum albumin of the three groups were not significantly different. Gains in length were significantly less for the experimental group than for the reference group. Serum urea nitrogen was significantly less in the experimental group than in the control group or reference group. We conclude that the protein-energy ratios of the experimental formula diet were below the safe level. Because the decrease in growth rate of the experimental group was rather small (demonstrable only in comparison with the large reference group), and because serum albumin of the experimental group increased with age as in normally nourished infants, we suspect that the safe protein-energy ratio of infant formulas lies closer to the ratios fed to the experimental group than to the ratio [approximately 5.0 g/MJ (2.1 g/100 kcal)] in currently marketed milk-based formulas.

Blood Urea Nitrogen

Fortification of human milk: evaluation of a novel fortification scheme and of a new fortifier.

Human milk fed to very-low-birth-weight infants must be fortified with protein, minerals, and vitamins. We tested a new fortification regimen in which the amount of fortifier was adjusted on the basis of frequent determinations of serum urea nitrogen (SUN). A newly formulated fortifier based on bovine milk proteins was employed either in the new fashion (regimen ADJ) or in the conventional fixed proportion (regimen FIX). Using the fixed proportion, the study also compared the new fortifier with a fortifier based on human milk protein (regimen HMP). Twelve infants were studied with each of the three regimens; nearly all completed 3 weeks of study. Protein intake was generally higher in ADJ than FIX; the difference was significant (p < 0.01) during week 2. Weight gain was somewhat (but not significantly) greater in regimen ADJ (32.3 g/d or 18.8 g/kg/d) than in regimen FIX (30.0 g/d or 18.3 g/kg/d). SUN was higher in ADJ than in FIX, and several other serum chemical values (calcium, phosphorus, potassium) tended to be higher, probably reflecting higher intakes of these nutrients with ADJ than with FIX. Plasma concentrations of several amino acids were higher in ADJ than FIX, but none, including threonine, were outside the physiological range. In comparing regimen FIX to regimen HMP, infants on FIX received similar intakes of protein and showed slightly but not significantly more rapid weight gain. Concentrations of SUN were lower with FIX, but other serum chemical values, including amino acids, were generally similar to HMP. We conclude that use of the new adjustable fortification regimen is feasible and safe and that it should be studied further. It produced the expected increases in nutrient intakes and growth. The new bovine milk-based fortifier appears to be equivalent to the human milk-based fortifier.

Amino Acids

The proportions of G gamma- and A gamma-globins in the fetal hemoglobin synthesized in preterm and term infants.

The change in G gamma to A gamma ratio in relation to the switchover of fetal HB (HbF) to adult Hb (alpha 2 beta 2) synthesis has not been well defined. The gamma-globins of HbF (alpha 2 gamma 2) have either glycine (G gamma) or alanine (A gamma) at position 136. During fetal life the G gamma makes up 70% of the gamma-globins, although they are 40% of the small amounts of HbF in the adult. To further the understanding of this switchover, globin chain synthesis was determined sequentially in eight preterm and 20 full-term infants postnatally. To complete the study, single analysis was also carried out in eight term infants at birth and six preterm infants at the postconceptional age equivalent to term. Blood samples were incubated in an amino acid mixture containing 3H-leucine and subjected to reversed-phase liquid chromatography. The results demonstrated that the fetal proportions of G gamma to A gamma are rigidly controlled according to postconceptional age and not affected by postnatal age after preterm birth. During the early postconceptional age switchover from HbF to adult Hb synthesis, an equal repression of the G gamma and A gamma chains was found. However, based on the values obtained from the term infants, after a postconceptional age of 44 wk, the levels of G gamma to total gamma synthesis begin to decrease and become more variable.

Fetal Hemoglobin

Erythrocyte incorporation of iron by 56-day-old infants fed a 58Fe-labeled supplement.

In an effort to obtain information about absorption of supplemental iron by breast-fed infants during the early months of life, we determined erythrocyte incorporation of a stable iron isotope, administered to 56-d-old breast-fed infants in the form of a 58Fe-labeled vitamin-iron supplement. Infants of similar age fed a milk-based formula low in iron (approximately 4 mg/L) were also studied. The 58Fe-labeled vitamin-iron supplement was given between feedings. Fourteen days after administration of 58Fe, mean erythrocyte incorporation of the isotope was 7.8% of the dose by breast-fed infants and 4.4% of the dose by formula-fed infants. The feeding-related difference was statistically significant, probably reflecting the greater quantities of inhibitors of iron absorption in the intestines of formula-fed infants. With mean iron intake from the 58Fe-labeled vitamin-iron supplement of 7.99 mg for the breast-fed infants, erythrocyte incorporation of 7.8% of the dose corresponded to 0.62 mg, a value in the range of the estimated requirement for absorbed iron. We conclude that 2-mo-old breast-fed infants are able to absorb nutritionally significant amounts of iron from an iron supplement.

Breast Feeding

Absorption and retention of dietary and supplemental fluoride by infants.

There is a widespread belief that an adequate intake of fluoride during the pre-eruptive stage of enamel formation (i.e., from the diet in frequent small doses throughout the day) will be protective against caries in later life. To obtain data on bio-availability and retention of fluoride in one age group (infants), we studied 3 treatment regimens: In Regimen A, small amounts of fluoride were obtained from the diet in frequent doses throughout the day; in Regimen B, a fluoride supplement (0.25 mg) was given once each day with a feeding; Regimen C was similar to regimen B except that the fluoride supplement was given 1 h before a feeding. For the 3 regimens, the respective mean absorptions of fluoride were 90.1, 88.9, and 96.0% of intake, and the respective retentions were 12.5, 47.1, and 52.3% of intake. Neither the difference in absorption nor the difference in retention between regimens B and C was statistically significant. By subtracting the background urinary excretion of fluoride (i.e., excretion of fluoride while diet was the sole source of fluoride) from the excretion after administration of the fluoride supplement, we calculated that 68.1% of the supplement was retained in Regimen B and 73.0% of the supplement in Regimen C. The difference was not significant.

Biological Availability

Fluoride pharmacokinetics in infancy.

Fluoride pharmacokinetic data are presented for infants given a fluoride supplement. Seventeen infants participated in a total of 20 studies. On one day, 0.013 mmol (0.25 mg) fluoride was given as a supplement (fluoride supplement study), and on another day a placebo was given (control study). Samples of plasma and urine were collected for 5 h and analyzed for fluoride. During control studies fluoride intake averaged 0.15 mumol/kg (2.9 micrograms/kg), and plasma fluoride concentrations ranged from 0.05 to 0.11 mumol/L (10 to 20 micrograms/L). In nine instances, the quantity of fluoride excreted in the urine was more than twice that consumed. When the fluoride supplement was given, total fluoride intake averaged 1.93 mumol/kg (36.6 micrograms/kg). Plasma peak concentration was reached by 30 min in 14 studies and by 60 min in six studies. Mean plasma peak fluoride concentration was 3.3 mumol/L (63 ng/mL). Area under the plasma concentration curve averaged 236 nmol.m-1 x min (4479 ng.mL-1 x min) and was not related to the dose of fluoride. The rate of urinary excretion was significantly correlated with rate of urinary flow. When the dose of fluoride was expressed per unit of body weight, fluoride retention was strongly related to the dose. Retention of the fluoride absorbed from the fluoride dose ranged from 75.4 to 87.6%. Plasma clearance averaged 6.8 mL.kg-1 x min-1 and decreased significantly with age. Net fractional clearance (renal clearance of the fluoride dose/GFR) averaged 56.7%, which was significantly greater than the 29% observed during the control studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Dental Caries

Erythrocyte incorporation of ingested 58Fe by 56-day-old breast-fed and formula-fed infants.

As an index of iron absorption, erythrocyte incorporation of the stable isotope, 58Fe, was determined 14 and 42 d after the administration of 58Fe-labeled ferrous sulfate to 56-d-old exclusively breast-fed infants and to infants fed a low-iron (1.8 mg/L) formula. Each infant received a dose of 0.6 to 1.0 mg of iron with ascorbic acid between feedings on each of 3 consecutive d. Fourteen d after administration of the 58Fe-labeled iron doses (age 70 d), arithmetic mean incorporation of the 58Fe label into erythrocytes by breast-fed infants was 20.0% of the dose--only slightly less than that reported for erythrocyte incorporation of iron by fasting adults fed small quantities of 59Fe-labeled human milk. Erythrocyte incorporation of iron by the formula-fed infants was 6.9% of the dose, suggesting that, even between feedings, components of infant formula exerted a major inhibitory effect on iron absorption. For reasons that are not clear, the percentage of the administered label incorporated into erythrocytes was significantly greater in breast-fed (but not in formula-fed infants) at 112 d of age than at 70 d of age.

Absorption

Reference data on gains in weight and length during the first two years of life.

Serial data from studies of infants at the University of Iowa and from the Fels Longitudinal Study were used to develop sex-specific percentiles for increments in weight and recumbent length for selected intervals during the first 24 months of life. Weight increments are presented for 1-month intervals from birth to 6 months, 2-month intervals from birth to 12 months, and 3-month intervals from birth to 24 months. Length increments are presented for 2-month intervals from birth to 6 months, and for 3-month intervals from birth to 24 months of age. Weights and lengths at the target ages were obtained for the Iowa data by simple interpolation, and for the Fels data by fitting families of three-parameter mathematical functions to the serial data from ages 1 to 24 months. The tabular presentations are based on the Iowa data from birth to 3 months of age, on the combined Iowa and Fels data from 3 to 6 months of age, and on the Fels data from 6 to 24 months of age. We believe that these reference data will be useful in screening for deviations from normal growth and may aid in early detection of failure to thrive or excessive weight gain during early life.

Age Factors

Plasma amino acid concentrations and amino acid ratios in normal adults and adults heterozygous for phenylketonuria ingesting a hamburger and milk shake meal.

Plasma amino acid concentrations were measured and selected amino acid ratios were calculated in 12 normal adults and 12 adults heterozygous for phenylketonuria (PKU) ingesting a hamburger and milk shake meal providing 1 g protein/kg body wt. Plasma concentrations of all amino acids increased significantly over baseline after meal ingestion in both groups, reaching the highest mean values 3-5 h after meal ingestion. Plasma phenylalanine concentrations were significantly higher in heterozygous than in normal subjects both before and at all times after meal ingestion. The absolute increase in plasma phenylalanine concentration over baseline and the area under the plasma phenylalanine concentration-time curve were approximately twice as large in heterozygous as in normal subjects. However, the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids did not increase significantly over baseline, but rather decreased.

Amino Acids

Malnutrition in the premature infant.

During the first few days of life, the ill premature infant is usually subjected to acute semistarvation because the provision of nutritional support is considered cumbersome and unnecessary. However, the absence of readily recognizable adverse effects of semistarvation does not rule out the existence of significant short-term adverse effects, nor does it rule out possible adverse sequelae in the long run. Similar concerns pertain to the later neonatal period, during which nutritional deprivation is less severe but of longer duration. Evidence is presented that qualitative malnutrition, characterized by inadequate intake of protein and relatively excessive intake of energy, is common with current feeding regimens and is responsible for increased body fat deposition in growing small premature infants.

Energy Intake

Repeated ingestion of aspartame-sweetened beverages: further observations in individuals heterozygous for phenylketonuria.

Six adults heterozygous for phenylketonuria (PKU) ingested eight successive servings of unsweetened and aspartame (APM)-sweetened beverage at 1-hour intervals in a randomized, balanced, crossover design. In one part, the eight beverage servings were not sweetened. In the other, each of the eight beverage servings provided 600 mg of APM, a dose equivalent to the amount provided by 36 oz of an APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine concentrations 2.35 to 4.03 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady-state after administration of five servings of APM-sweetened beverage and were slightly, but significantly higher than usual postprandial values for adults heterozygous for PKU. Similarly, the ratio of the plasma phenylalanine concentration to the sum of the concentration of the large neutral amino acids was significantly higher than usual postprandial values. Blood methanol and formate concentrations remained within normal limits. These data indicate that a fasting adult heterozygous for PKU could consume the equivalent of 24 12-oz servings of APM-sweetened beverage over an 8-hour period and only increase plasma phenylalanine concentration to a modest degree.

Adult

Aspartame ingestion with and without carbohydrate in phenylketonuric and normal subjects: effect on plasma concentrations of amino acids, glucose, and insulin.

Seven subjects homozygous for phenylketonuria (PKU) and seven normal subjects were administered four beverage regimens after an overnight fast: unsweetened beverage, beverage providing carbohydrate (CHO), beverage providing aspartame (APM), and beverage providing APM plus CHO. The APM dose (200 mg) was the amount provided in 12 oz of diet beverage; the CHO was partially hydrolyzed starch (60 g). Plasma amino acid concentrations were determined after dosing and the molar plasma phenylalanine (Phe) to large neutral amino acid (LNAA) ratio calculated. APM administration without CHO did not increase plasma Phe concentrations over baseline values in either normal or PKU subjects (5.48 +/- 0.85 and 150 +/- 23.0 mumols/dL, respectively). Similarly, the Phe/LNAA did not increase significantly. Ingestion of beverage providing APM and CHO did not significantly increase plasma Phe concentrations over baseline values in either normal or PKU subjects. However, ingestion of beverage providing CHO (with or without APM) significantly decreased plasma levels of valine, isoleucine, and leucine 1.5 to 4 hours after dosing in both normal and PKU subjects, thereby increasing the Phe/LNAA ratio significantly. These data indicate that changes noted in Phe/LNAA values after ingestion of beverage providing APM plus CHO were due to CHO. The plasma insulin response to beverage providing CHO (with or without APM) was significantly higher in PKU subjects than in normals.

Adolescent

Milks and formulas for older infants.

Older infants derive a substantial proportion of their nutrient intake from beikost (foods other than milk or formula). Milks and formulas fed to older infants should complement the nutrient intake provided by beikost without unduly stressing the infant's capacity to excrete waste products. Using contemporary data regarding nutrient intakes from beikost, I examined the total nutrient intake of 6- to 12-month-old infants. Nutrient intakes of infants fed beikost plus iron-fortified formulas designed for younger infants are entirely satisfactory. On the other hand, when cow milk is fed together with beikost, infants receive unnecessarily high intakes of protein and electrolytes, resulting in an unduly high renal solute load. Because cow milk is also prone to cause occult intestinal blood loss, it is not considered a suitable feeding for 6- to 12-month-old infants.

Animals

Formulas for older infants.

We explored the possibility that standard infant formulas designed as the sole source of nutrients for small, rapidly growing infants may not be equally suitable for older, larger, and less rapidly growing infants who obtain a portion of energy intake from beikost. Our approach was to consider the probable nutrient intakes of a 6-month-old hypothetic infant receiving 80% of energy intake from a standard formula and 20% from beikost, and nutrient intakes of a 10-month-old hypothetic infant receiving 50% of energy intake from a standard formula and 50% from beikost. The assortment of beikost items consumed by infants is moderately high in protein and low in fat. Calculated nutrient intakes of the 10-month-old hypothetic infant were compared with intakes of infants of similar age in two national surveys. We conclude that standard infant formulas designed for young infants are reasonably well suited to meeting the nutrient needs of infants during the latter half of the first year of life.

Aging

Cow milk feeding in infancy: further observations on blood loss from the gastrointestinal tract.

Because feeding of cow milk causes normal infants to lose increased amounts of occult blood from the gastrointestinal tract, we conducted a prospective trial to measure intestinal blood loss quantitatively and to monitor iron nutritional status. Fifty-two infants entered the trial at 168 days of age and were assigned at random to receive either cow milk or a milk-based formula. Initially, 31 infants had been breast-fed and 21 had been fed formulas. With the feeding of cow milk, the proportion of guaiac-positive stools increased from 3.0% at baseline to 30.3% during the first 28 days of the trial (p less than 0.01), whereas the proportion of positive stools remained low (5.0%) with the feeding of formula. The proportion of guaiac-positive stools among cow milk-fed infants declined later, but for the entire trial it remained significantly (p less than 0.01) elevated. Stool hemoglobin concentration increased markedly with the introduction of cow milk, rising from a mean (+/- SD) of 622 +/- 527 micrograms/gm dry stool at baseline to 3598 +/- 10,479 micrograms/gm dry stool during the first 28 days of ingestion of cow milk. Among infants fed formula, stool hemoglobin did not increase and was significantly (p less than 0.01) less than in the cow milk group. Among infants fed cow milk, the increase in hemoglobin concentration tended to be greater for those who had initially been fed human milk than for those who had initially been fed formulas. Iron nutritional status was not significantly different between the two feeding groups. However, one infant became iron deficient after 4 weeks of ingesting cow milk. We conclude that cow milk feeding leads to increased intestinal tract blood loss in a large proportion of normal infants and that the amount of iron lost is nutritionally important.

Animals

Effect of sucrose on the metabolic disposition of aspartame.

Twelve normal adult subjects ingested a beverage providing 0.136 mmol aspartame/kg body wt on 2 different days. On 1 study day the beverage provided only aspartame, on the other the beverage provided both aspartame and 3.51 mmol sucrose/kg body wt. The high mean plasma phenylalanine concentrations were similar after administration of aspartame alone (158 +/- 28.9 mumol/L, mean +/- SD) and administration of aspartame plus sucrose (134 +/- 44.1 mumol/L). Evaluation of the area under the plasma concentration-time curve (AUC) for phenylalanine also showed no significant difference between groups (197 +/- 49.1 vs 182 +/- 28.3 mumol.L-1.h for aspartame alone and aspartame plus sucrose, respectively). Similarly, the high mean ratio of phenylalanine to large neutral amino acids (Phe:LNAA) in plasma did not differ significantly (0.265 +/- 0.046 for aspartame alone, 0.275 +/- 0.107 for aspartame plus sucrose). However, there was a small but significant difference between groups for the 4-h AUC values for plasma Phe:LNAA. The simultaneous ingestion of sucrose with aspartame had only minor effects on aspartame's metabolic disposition.

Adult

Feasibility of using the stable isotope 25Mg to study Mg metabolism in infants.

The feasibility of using isotopic techniques to study Mg absorption and metabolism was explored in three full-term human infants. 25Mg (98.8 atom %) was administered orally as an in vivo tracer. Fractional 25Mg absorption, isotope retention, endogenous fecal Mg losses, and apparent Mg exchangeable pool size were then determined under three conditions of isotope administration: 1) 20 mg 25Mg, with single feeding; 2) 20 mg 25Mg, distributed over a 24-h period; and 3) 60 mg 25Mg, over a 24-h period. Mg isotope ratios were determined by inductively coupled plasma mass spectrometry. Fractional absorption was increased in all three infants after distributed versus bolus administration at the 20 mg dose; mean (+/- SD) fractional absorption was 64.0 +/- 3.9 versus 54.3 +/- 5.9%, respectively. 25Mg retention was also more in all three infants after distributed administration (55.8 +/- 3.0 versus 44.3 +/- 1.3% of dose). At the 60-mg 25Mg dose, compared to 20 mg, fractional absorption was reduced but absolute isotope absorption more than doubled in all infants; urine isotope losses represented a similar fraction of the absorbed dose, thus, 25Mg retention also more than doubled. Compared to the results of the isotope studies, net Mg absorption and balance were uninfluenced by total Mg intake. Isotope retention with distributed isotope administration resulted in measurable isotopic enrichment of plasma and erythrocytes at 72 h (i.e. plasma isotope enrichment was 6.3-10.2 and 19.2-23.5% for the 20- and 60-mg dose, respectively). With these doses, apparent Mg exchangeable pool size ranged from 5.5 to 7.6 mmol/kg body wt; these values showed a decrease with age both within and between infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Feasibility Studies

Effect of repeated ingestion of aspartame-sweetened beverage on plasma amino acid, blood methanol, and blood formate concentrations in normal adults.

Aspartame (APM) is a widely used dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester). It has been suggested that excessive use of APM might elevate plasma aspartate, phenylalanine, and/or methanol concentrations to levels that are potentially harmful. Six normal young adults ingested eight successive servings of unsweetened and APM-sweetened beverage at one-hour intervals in a balanced crossover design. In one part, the beverage was not sweetened. In the other, each serving of beverage provided 600 mg APM, a dose equivalent to the amount provided by 36 oz of APM-sweetened diet beverage. Plasma aspartate concentration was not significantly increased after ingestion of unsweetened or APM-sweetened beverage. Similarly, ingestion of the unsweetened beverage had no significant effect on plasma phenylalanine concentration. However, ingestion of APM-sweetened beverage significantly increased plasma phenylalanine levels 1.41 to 2.35 mumol/dL above baseline 30 minutes after ingestion. Plasma phenylalanine values reached a steady state after administration of four to five servings and did not exceed normal postprandial values at any time. Blood methanol and formate concentrations remained within normal limits. The data indicate ready metabolism of APM when administered at levels that may be ingested by normal individuals who are heavy users of diet beverages.

Adult