Milk protein intake in the term infant. II. Effects on plasma amino acid concentrations

The response of plasma amino acids to two bovine protein formulas with different protein content (1.6 and 1.2 g/100 ml containing 60% whey proteins and 40% caseins) was measured in term infants. These two groups of infants were compared with a group of infants that were breast-fed; all infants were fed ad libitum. Concentrations of threonine, valine and total branched chain amino acids reflected the amount of protein provided. Thus, the concentrations were higher in the higher protein formula infants from the second week of the study. In the low protein formula infants these amino acids were lower but differed from the infants on breast milk at eight and twelve weeks. Concentration of taurine was lower in the formula fed infants than they were in breast-fed infants at the end of the study. The valine/glycine ratio in the low protein formula group was lower than in the breast-fed group for the first four weeks of the study. After this time it was equal to that of the breast-fed group. These differences in plasma amino acid concentrations give further evidence that formulas now in common use for term infants provide a protein intake in excess of protein requirements after the first months of life.     

Amino Acid Levels in the Critically ill Preterm Infant Given Mother's Milk Fortified with Protein from Human or Cow's Milk

ABSTRACT. Twenty preterm infants undergoing neonatal intensive care were randomly allocated to one of two feeding regimens: human milk enriched with either human milk protein (HMP) or adapted cow's milk protein (CMP). The birthweights (1076 ± 301 g; 1031 ± 309 g) and the gestational ages (28.4 ± 1.6 weeks; 27.7 ± 2.1 weeks) were comparable. The amount of protein added to the milk was set at 0.7 g/100 ml in order to provide a total supply of 3.0-3.5 g/kg/24 h. All infants received additional amounts of carbohydrate, calcium, phosphorous, and sodium chloride. Capillary whole blood amino acids were measured with high pressure liquid chromatography (HPLC). The amino acid levels did not differ significantly when the feeding groups were compared week by week, but the glycine/valine ratio was higher (p<0.05) in the HMP group after three weeks of fortification. Longitudinal changes after protein enrichment could be demonstrated in both groups. Alanine and threonine increased after one week (p<0.01) in both groups. Glycine in the HMP group peaked after two weeks (p<0.02), and valine in the CMP group increased (p<0.02) after one week on the feeding regimen. However, the amino acids never reached levels above those seen after a meal in normal term newborns. Other variables related to protein intake, such as protein and urea in serum, did not vary between the groups. Growth, expressed as gains in weight, length, and head circumference was poor but comparable. The quality of the protein, whether a human milk protein isolate or a cow's milk whey protein product, used for the fortification of human milk up to a protein load of 3.0-3.5 g/kg/24 h, did not cause any alterations of significance in the amino acid profiles of peripheral blood.     

PLASMA FREE AMINO ACID CONCENTRATIONS OF BREAST-FED INFANTS

ABSTRACT. Photometric determination of alpha-amino nitrogen in peripheral venous plasma and urine from 20 healthy, full-term infants, 1–5 months of age, showing normal growth and development during an uncomplicated lactation, revealed lower plasma levels than what has been found in adults, or 3.7±1.1 mg/100 ml, and a urinary excretion of 41 + 14 mg/24 hours. Ion-exchange chromatography of deproteinized peripheral venous plasma showed low valine concentrations, an increased glycine/valine ratio and high cystine and very high taurine levels when compared to the levels of healthy American infants of comparable ages fed 3-3.5 g/kg of cow-milk protein. The findings indicate that a formula based on cow-milk protein should optimally contain only 1.0–1.2 g protein/100 ml provided that it is "humanized" not only with regard to the lactalbumin/casein ratio, but also to the cystine and taurine content. The pattern of the plasma concentrations of free amino acids reported in the present investigation may be used as a normal reference for breast-fed infants.     

Indices of protein metabolism in term infants fed either human milk or formulas with reduced protein concentration and various whey/casein ratios

Hyperaminoacidemia is evident in infants fed either whey-dominant or casein-dominant formula containing 2.2 g protein/100 kcal. We assessed protein metabolism in infants fed formulas with reduced protein contents and various whey/casein ratios. Term infants (n = 40) received either human milk or formula containing 1.8 g protein/100 kcal and whey/casein ratios 18:82, 34:66, or 50:50. At ages 4 and 8 weeks, growth indices and mean serum concentrations of retinol binding protein, albumin, total protein, and serum urea nitrogen were similar, as were mean plasma concentrations of total amino acids, total essential amino acids, and their ratio. Compared with infants fed human milk, those fed formula had plasma concentrations similar for valine, lysine, arginine, tyrosine, histidine, threonine, and free and total cyst(e)ine; elevated for phenylalanine, methionine, and citrulline; and depressed for taurine and tryptophan. Except for leucine, mean plasma amino acid values varied similarly among formula groups despite differences in intakes. Our data indicate that feeding formulas providing 1.8 g protein/100 kcal results in many indices of protein metabolism characteristic of human milk feeding. However, certain differences are noted, suggesting the need for further manipulation of specific amino acid patterns of infant formulas.     

Plasma free amino acid concentrations of breast-fed infants

Photometric determination of alpha-amino nitrogen in peripheral venous plasma and urine from 20 healthy, full-term infants, 1--5 months of age, showing normal growth and development during an uncomplicated lactation, revealed lower plasma levels than what has been found in adults, or 3.7 +/- 1.1 mg/100 ml, and a urinary excretion of 41 +/- 14 mg/24 hours. Ion-exchange chromatography of deproteinized peripheral venous plasma showed low valine concentrations, an increased glycine/valine ratio and high cystine and very high taurine levels when compared to the levels of healthy American infants of comparable ages fed 3--3.5 g/kg of cow-milk protein. The findings indicate that a formula based on cow-milk protein should optimally contain only 1.0--1.2 g protein/100 ml provided that it is "humanized" not only with regard to the lactalbumin/casein ratio, but also to the cystine and taurine content. The pattern of the plasma concentrations of free amino acids reported in the present investigation may be used as a normal reference for breast-fed infants.     

Plasma amino acids after a feed of human milk or formula at three months of age

Prefeeding plasma amino acid concentrations were higher and glycine-to-valine ratios lower in formula-fed infants as compared to breast-fed infants at 3 months of age. After a human milk meal (true protein, 0.8 g/100 ml) or formula meal (1.5 g/100 ml), all essential and several nonessential amino acids peaked at 30-60 min. The postprandial increments were greater and lasted longer after formula, reflecting the amounts of individual amino acids in the feeds. The changes resembled those seen in adults, and were smaller than those observed in these infants at 1 week of age. These data indicate that gastrointestinal, hepatic, and endocrine responses to a meal are immature at the age of 3 months.     

Milk protein quality in low birth weight infants: effects of protein-fortified human milk and formulas with three different whey-to-casein ratios on growth and plasma amino acid profiles.

Growth rates (weight, length, and head circumference) and selected biochemical indexes of protein metabolism (serum urea, acid-base status, and plasma amino acid concentrations) were determined in low birth weight (LBW) infants appropriate for gestational age (birth weight less than 1,650 g) fed three formulas differing only in the whey-to-casein ratios: 60/40, 50/50, and 35/65. A group of infants fed exclusively human milk protein (HMP)-fortified human milk was used as a control. All diets provided similar daily protein and energy intakes, which were 3.5 g/kg and 122 kcal/kg in the human milk-fed infants and 3.3 g/kg and 121 kcal/kg in the formula-fed infants. Neither weight gain nor rate of growth in length and head circumference differed between the feeding groups and reached intrauterine or better rates in all groups. Values for serum urea and acid-base status were normal and also did not differ among the groups. At the end of the study, plasma threonine concentrations were significantly higher in all formula-fed infants than in the infants fed human milk. The highest plasma threonine concentration was found in the infants receiving the whey-predominant formula. Plasma concentrations of valine, methionine, and phenylalanine were also significantly higher in all formula-fed groups when compared with the human milk group. Plasma total essential amino acid concentrations were also significantly higher in the formula-fed infants than in the human milk fed. The results show that protein quality does not affect growth rate or biochemical indexes of metabolic tolerance in LBW infants fed adequate protein and energy intakes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postprandial plasma amino acids in preterm infants: influence of the protein source

Preprandial plasma amino acid concentrations have been used extensively as a marker of the nutritional value of dietary proteins in preterm infants. This study investigated the postprandial plasma amino acid profiles of preterm infants fed with different dietary proteins at similar protein intakes during the first weeks of life. In 12 preterm infants, pre- and postprandial plasma amino acid concentrations were measured before the removal of an indwelling central venous catheter placed for parenteral nutrition. All infants received breast milk until the time of study. At the start day of the study, infants were randomized to receive a test meal of 10 ml/kg, either of breast milk fortified with breast milk protein to reach a protein content of 2.0 g/dl or of a bovine milk preterm formula with a protein content of 2.0 g/dl (whey/casein ratio 60/40). Five samples of 100 microl blood were obtained immediately before and 15, 30, 45 and 60 min after the test meal. The plasma amino acid analysis was performed by a reversed-phase high-performance liquid chromatography based on o-phthaldialdehyde/2-mercaptoethanol pre-column derivatization. In both groups, the plasma amino acid concentrations increased within the first 30 min and the levels did not return to the preprandial baseline during the observation period. Fifteen minutes after the test meal, the plasma levels of all essential amino acids with the exception of histidine were higher in the bovine milk formula fed infants than in the fortified breast milk fed infants. The sum of plasma essential amino acid levels found in the formula fed infants were significantly (p < 0.05) higher than the levels found in the fortified breast milk fed infants at 15, 30 and 45 min. The kinetics of individual amino acids were influenced by the different quality of the protein even when the intakes in the groups were similar, as demonstrated for histidine and phenylalanine. The data indicate that postprandial plasma amino acid concentrations depend significantly on the dietary amino acid source and cannot simply be calculated from the amino acid composition of dietary proteins. Therefore, postprandial plasma amino acid concentrations should be included in the nutritional evaluation of dietary proteins in preterm infants.     

Protein and Energy Intake during Weaning

ABSTRACT. Preprandial plasma amino acid concentrations were measured at 5 and 6 months of age in 30 healthy term infants who were either breast-fed ad libitum or fed one of two different formulas (1.9 g of protein per 100 ml with a whey: casein ratio of 50:50; 2.9 g of protein per 100 ml with a whey: casein ratio of 20:80) ad libitum, plus the same supplementary food regimen. The mean plasma concentrations of total amino acids and especially total essential amino acids were higher in the formula-fed infants. Those fed formula also had plasma concentrations of methionine, isoleucine, phenylalanine, leucine, valine, threonine, aspartate, proline, lysine, tyrosine, histidine that exceeded plasma concentrations of breast-fed infants by 2 or more standard deviations. Concentrations of arginine, glutamic acid, glutamine, ornithine, serine, cystine did not differ and taurine was higher in the breast-fed infants. The data indicate that formulas in common use today during weaning (4–6 months) provide excessive protein intakes when compared to the breast-fed control infants. A lowering of protein concentration and a further manipulation of the whey: casein ratio is necessary if plasma amino acid patterns similar to those found in breast-fed infants is to be achieved with artificial feeding.     

Protein and energy intake during weaning. III. Effects on plasma amino acids

Preprandial plasma amino acid concentrations were measured at 5 and 6 months of age in 30 healthy term infants who were either breast-fed ad libitum or fed one of two different formulas (1.9 g of protein per 100 ml with a whey:casein ratio of 50:50; 2.9 g of protein per 100 ml with a whey:casein ratio of 20:80) ad libitum, plus the same supplementary food regimen. The mean plasma concentrations of total amino acids and especially total essential amino acids were higher in the formula-fed infants. Those fed formula also had plasma concentrations of methionine, isoleucine, phenylalanine, leucine, valine, threonine, aspartate, proline, lysine, tyrosine, histidine that exceeded plasma concentrations of breast-fed infants by 2 or more standard deviations. Concentrations of arginine, glutamic acid, glutamine, ornithine, serine, cystine did not differ and taurine was higher in the breast-fed infants. The data indicate that formulas in common use today during weaning (4-6 months) provide excessive protein intakes when compared to the breast-fed control infants. A lowering of protein concentration and a further manipulation of the whey:casein ratio is necessary if plasma amino acid patterns similar to those found in breast-fed infants is to be achieved with artificial feeding.     

Growth, serum biochemistries, and amino acids of term infants fed formulas with amino acid and protein concentrations similar to human milk

We tested the hypothesis that amino acid intake from infant formulas modified to be similar to human milk would result in indices of protein metabolism more like those in human milk-fed infants. Formula-fed infants received for 12 weeks one of three isocaloric formulations of a whey-adapted formula that differed in protein concentration: 11, 13, or 15 g/L. Infants consumed similar volumes of formula or human milk. Serum urea nitrogen concentrations reflected the protein content of the diets. Plasma indices of protein nutritional status were normal and did not differ among groups. Growth rates of all infants were normal and similar. Serum indicators of protein nutritional status varied with age, which made comparisons of formula-fed infants with human milk-fed infants difficult. Plasma concentrations of leucine and isoleucine at 4 weeks of age were higher in infants fed the formula containing 15 g protein/L when compared with those of infants fed the other two formulas or human milk. At 8 and 12 weeks of age, all formula-fed infants had plasma amino acid profiles that did not differ significantly from each other except for isoleucine, which was lower in the 11-g/L group. We found that providing formulas with an amino acid pattern similar to that of human milk did not produce a plasma amino acid pattern identical to that of the breast-fed infant. This observation suggests that other factors, such as the hormonal response to feeding, differing nutritional bioavailability of amino acids from human and bovine milk proteins, and the changing quantity and type of amino acids with advancing lactation, influence plasma amino acid concentrations.     

Plasma amino acid differences in very low birth weight infants fed either human milk or whey-dominant cow milk formula

Midmorning plasma amino acid levels were measured in 31 healthy, very low birth weight infants (mean age 16 days, mean birth weight 1180 g, gestation 29 wk) during 96-h balance studies. All infants received continuous enteral infusion of isonitrogenous, isocaloric preparations of either human milk fortified with pasteurized, lyophilized fractions of mature human milk (n = 18) or whey-dominant cow milk-based formula (n = 13). Weight gain (15 g/kg/day), nitrogen retention (303 mg/kg/day), and metabolizable energy (104 kcal/kg/day) were similar between groups. Plasma levels of threonine, valine, and the sum of essential amino acids were significantly greater in the whey-dominant formula-fed infants (p less than 0.01). Taurine and cystine were measured in significantly greater concentrations in the fortified human milk and threonine, valine, methionine, and lysine in the whey-dominant cow milk formula (p less than 0.01). Relationships between plasma amino acid levels and indices of nitrogen utilization differed between groups. These differences suggest that further modifications of whey-dominant formulas may be indicated.     

Growth and metabolic responses in low-birth-weight infants fed human milk fortified with human milk protein or with a bovine milk protein preparation

Unfortified human milk does not normally provide enough protein to secure maximal growth in low-body-weight (LBW) infants. Due to the practical difficulties in obtaining human milk protein (HMP), a bovine milk protein preparation (BMP) was designed by computer calculation to contain as close as possible the amino acid composition of the nutritionally available human milk proteins. Twenty-one AGA, LBW infants (BW of 1,180 to 1,600 g, GA of 27 to 33 weeks) were randomly assigned to be fed HM enriched either with HMP (9 infants) or BMP (12 infants). When full volume intake (170 ml/kg/day) was reached, the protein intakes were 3.6 +/- 0.5 and 3.3 +/- 0.3 g/kg/day, respectively, in the two diet groups. During the study period of 24 days, the infants achieved intrauterine or better weight gains: 32.9 +/- 3.3 g/day (17.7 +/- 1.9 g/kg/day) in the HMP group and 34.7 +/- 7.3 g/day (18.3 +/- 3.5 g/kg/day) in the BMP group. Serum urea nitrogen, acid-base status, and albumin values were normal and similar in both groups of infants. Plasma concentrations of total essential and total amino acids at the end of the study were 3,999 and 1,539 mumol/L and 3,899 and 1,422 mumol/L in the HMP and the BMP groups, respectively. The concentrations of all individual plasma amino acids were similar in both feeding groups. These results show that feeding human milk fortified with a modified bovine milk protein preparation produces satisfactory growth and a plasma amino acid profile similar to that found in LBW infants fed exclusively human milk protein at similar intakes.     

Growth and plasma amino acid concentrations in very low birthweight infants fed either human milk protein fortified human milk or a whey-predominant formula

In a prospective, study involving 20 VLBW-infants (AGA), divided into two study groups of 10 infants, we have evaluated the effects on growth and metabolism of human milk fortified with ultrafiltrated human milk protein and a whey-predominant (whey/casein = 60/40) formula containing 2 g/dl of protein. The study was initiated at a mean age of 30 days when an oral intake of 180 ml/kg/d was tolerated and continued until a weight of 2 kg was reached. The protein intake in both groups was about 3.7 g/kg/d. All infants in both groups reached intrauterine rates of growth for the age, weight gain 18.0 g/kg/d, and length 1.2 cm/week. BUN, acid-base status, total protein and albumin were normal and similar in the two groups. Plasma levels of threonine, glycine, citrulline and methionine were significantly greater in the formula-fed infants. Taurine and proline had higher concentrations in the protein fortified human milk group. There was good tolerance of protein from both sources but the differences in plasma amino acid profiles suggest that the dietary protein quality in formulas for preterm infants must be further modified, if the goal of formula feeding is to achieve metabolic indices of protein metabolism similar to those found when human milk protein is used.     

THE PROTEIN TOLERANCE OF VERY LOW BIRTH WEIGHT INFANTS FED HUMAN MILK PROTEIN ENRICHED MOTHER'S MILK

ABSTRACT. Pooled breast milk was ultra-filtrated and freeze-dried to give a product with a protein content of 60 g/100 g powder. More than half of the secretory IgA activity against E. coli O antigen was preserved. This concentrated protein was added to the mother's fresh milk providing a protein supply of 3.0-3.5 g/kg/24 hours in four VLBW infants, at a calorie supply of 110 kca/kg/24 hours. Growth followed the intrauterine rate. Free amino acid levels, acid-base balance and urea concentrations of peripheral whole blood indicated tolerance of the increased supply of human milk protein.     

Indices of protein metabolism in term infants fed human milk, whey-predominant formula, or cow's milk formula

Relationships between intakes of amino acids and total nitrogen, and blood indices of protein utilization were studied in 37 term infants fed either human milk, whey-predominant formula, or cow's milk formula as the sole nutritional source for 8 weeks. Biochemical analyses of two-hour fasting blood samples, and intakes calculated using three-day dietary records and direct analyses of milk samples were used to evaluate these relationships. Intakes of total nitrogen were positively correlated with plasma valine, leucine, isoleucine, phenylalanine, and serum urea nitrogen concentrations (r = .46 to .62, P less than .01 to .001). Intakes of the four amino acids whose plasma concentrations were positively correlated with total nitrogen intakes plus four additional amino acids (threonine, tyrosine, histidine, and methionine) were correlated with their respective plasma concentrations (r = .41 to .74, P less than .01 to .001). These relationships have not been previously described in term infants. Compared with values in infants fed human milk, plasma concentrations of valine, phenylalanine, methionine, and serum urea nitrogen were elevated with whey-predominant formula and cow's milk formula feeding. Values for four additional amino acids (threonine, lysine, leucine, and isoleucine) were elevated with whey-predominant formula feeding. Data indicate that altering the whey-to-casein ratio and, thus, the amino acid pattern of formulas will not achieve the desired blood indices characteristic of human milk feeding without a reduction in the total nitrogen content of formulas.     

Tryptophan fortification of adapted formula increases plasma tryptophan concentrations to levels not different from those found in breast-fed infants.

Several recent studies have demonstrated significantly lower plasma total tryptophan concentrations in formula-fed than in breast-fed infants. We have measured preprandial plasma amino acid concentrations in infants breast-fed or fed a formula with a protein concentration of 1.57 g/dl and with a whey/casein ratio of 60:40 or a formula with a protein concentration of 1.37 g/dl and a whey/casein ratio of 40:60 and fortified with 10 mg/dl (15 mg/100 kcal) of tryptophan. Healthy term infants (10 per group) were either breast-fed from birth or randomly assigned to one of the two study formulas. At 4 and 12 weeks of age, anthropometric measurements were performed and blood samples were obtained. During the study period of 12 weeks, all infants showed normal growth (weight, length, and head circumference) and there were no statistically significant differences between the groups. The plasma concentrations of the essential amino acids phenylalanine, threonine, valine, and lysine were significantly lower in the breast-fed group than in both formula-fed groups. For tyrosine, methionine, leucine, histidine, isoleucine, and arginine, no significant differences could be found between the feeding groups. Concentration of total plasma tryptophan was significantly higher in the breast-fed group than in the group fed the tryptophan-unfortified formula, but no statistically significant difference could be found between the plasma tryptophan concentration in the breast-fed group versus the group fed the tryptophan-fortified formula. The results indicate that tryptophan fortification of adapted formula is necessary to achieve plasma total tryptophan concentrations similar to those found in breast-fed infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperaminoacidemia due to the accumulation of gluconeogenic amino acid precursors in hypoglycemic small-for-gestational age infants.

The postnatal (3 to 12 hours) plasma amino acid patterns of normal full-term, nonhypoglycemic, and hypoglycemic small-for-gestational age infants were compared. Seventeen amino acid were separated by automatic column chromatography. It was found that hypoglycemia in SGA newborn infants was associated with a marked increase in total serum amino acid concentrations. This hyperaminoacidemia, which was mainly due to the increase in concentrations of alanine, glycine, proline, and valine, apparently reflected a decreased heapatic gluconeogenic capacity. A significant inverse correlation was observed between concentration of blood glucose and the accumulation of gluconeogenic amino acids. The proportionate accumulation of alanine, glycine, proline, and valine suggests a closely interrelated production and release of these amino acids from the peripheral pools. It is concluded that the changes in concentrations of plasma amino acids occurring in hypoglycemic SGA infants can be helpful in understanding the relative contribution of individual amino acids to gluconeogenesis in the human infant.     

Growth and Plasma Amino Acid Concentrations in Very Low Birthweight Infants Fed Either Human Milk Protein Fortified Human Milk or a Whey-Predominant Formula

ABSTRACT. In a prospective, study involving 20 VLBW-infants (AGA), divided into two study groups of 10 infants, we have evaluated the effects on growth and metabolism of human milk fortified with ultrafiltrated human milk protein and a whey-predominant (whey/ casein = 60/40) formula containing 2 g/dl of protein. The study was initiated at a mean age of 30 days when an oral intake of 180 ml/kg/d was tolerated and continued until a weight of 2 kg was reached. The protein intake in both groups was about 3.7 g/kg/d. All infants in both groups reached intrauterine rates of growth for the age, weight gain 18.0 g/kg/d, and length 1.2 cm/week. BUN, acid-base status, total protein and albumin were normal and similar in the two groups. Plasma levels of threonine, glycine, citrulline and methionine were significantly greater in the formula-fed infants. Taurine and proline had higher concentrations in the protein fortified human milk group. There was good tolerance of protein from both sources but the differences in plasma amino acid profiles suggest that the dietary protein quality in formulas for preterm infants must be further modified, if the goal of formula feeding is to achieve metabolic indices of protein metabolism similar to those found when human milk protein is used.     

Nutrition of very low birth-weight premature infants with enriched breast milk during the adjustment phase

To enable an enteral nutrition in very low birth weight infants appropriate for gestational age, adapted to the high nutritional requirements, pooled human milk from mothers delivered preterm was enriched with human milk lyophilisate 6 g/100 ml. The concentrations of protein increase from 11.8 +/- 1.2 to 15.8 +/- 2.1 g/l and the non-protein energy substrates raise in the same proportion. Osmolality increases from 291.6 +/- 11.2 to 384.9 +/- 19.6 mosmol/l. The higher protein intake was tolerated without relevant metabolic imbalances. Only small increasing of amino acids concentrations in serum and a higher renal excretion of amino acids could be observed. The nitrogen balance was equalized during the first two days of life and positive from the 3rd day of life. Nitrogen retention was significantly higher in the group fed human milk lyophilisate enriched human milk from the 2nd day of life. Also the postnatal weight losses were significantly lower and the birth weight was reached significantly earlier. Human milk lyophilisate enriched human milk can be recommended for nutrition of very low birth weight infants appropriate for gestational age from the first day of life.