Cysteine supplementation increases glutathione, but not polyamine, concentrations of the small intestine and colon of parenterally fed newborn rabbits.

The glutathione precursor cysteine is not contained in most total parenteral nutrition (TPN) formulations, and premature infants may not be capable of synthesizing cysteine because of a deficiency of cystathionase. Glutathione depletion may have negative effects on host defense against oxidative damage. Several studies have suggested that glutathione depletion induces ornithine decarboxylase activity and increases in polyamine concentrations. Since an inverse relationship between polyamine and glutathione concentrations has been suggested, the concentrations of both of these compounds may be altered in premature infants receiving TPN. We measured glutathione and polyamine concentrations of the small intestine and colon of prematurely delivered newborn rabbits administered TPN for 7 days after birth with or without added cysteine (75 or 150 mg kg-1 day-1). Maternally reared kits were also studied. Total glutathione concentrations in the gastrointestinal tract were significantly lower in kits administered cysteine-free TPN than in kits receiving cysteine or who were maternally reared. Polyamine concentrations did not differ among groups. Glutathione depletion of the small intestine and colon does occur during cysteine-free parenteral nutrition and may compromise intestinal defense against oxidant damage.

Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups.

Barker recently hypothesized that factors affecting prenatal and infant growth are related to adult blood pressure and CVD mortality. Predictions from Barker's hypothesis in regard to infant feeding were tested among a sample of 3 or 4 year old children. The relationship of infant-feeding characteristics (duration of breast-feeding, times of introduction of high fat, high carbohydrate, high potassium foods and table salt) to indicators of cardiovascular functioning (resting blood pressures and heart rates, and heart rate response to graded activity) while controlling for anthropometric (height, sum of seven skinfolds, BMI) and demographic (ethnicity, gender, social status) characteristics revealed that infant-feeding practices were not related to CV functioning in the predicted directions among this sample of 3 or 4 year old children. Furthermore, the positive relationship between height and systolic blood pressure was inconsistent with the Barker hypothesis.

Amino acid responses to dietary intake in the first 72 hours of life.

Plasma free amino acid concentrations were measured in cord blood and at 24, 48, and 72h of age in term infants who were either breastfed or fed a whey- or casein-predominant standard term-infant formula. There was a significant initial decrease in the concentrations of almost all amino acids compared with cord blood. Statistically significant effects of the type of feeding were observed in the concentrations of methionine, cystine, tyrosine, alanine, and p-serine; similarly, significant effects of postnatal age were noted in the concentrations of all amino acids with the exception of cystine. These data suggest that the metabolic milieu changes rapidly after delivery, influenced both by postnatal age and by type of feeding. Cord blood urea and histidine concentrations were significantly higher in female infants than in male infants; the route of delivery (cesarean section v vaginal delivery) affected only cord blood concentrations of alanine (vaginal greater than C-section). These data suggest that amino acid responses to the quality of dietary protein observed in infancy (for example, high tyrosine concentrations in response to feeding a casein-predominant formula) develop in the immediate postnatal period.

Taurine and cholesterol supplementation in the term infant: responses of growth and metabolism.

The effects of taurine and of cholesterol supplementation to a whey-protein-predominant formula fed ad libitum on the growth and biochemical responses of term infants were studied. The responses of these infants were compared to those of infants fed formula without a supplement and infants that were breastfed. These infants were followed for 12 weeks. No effect of cholesterol was observed on any of the measurements and no effect of taurine was observed on any of the biochemical measures with the exception that taurine concentrations in plasma and urine (reduced in infants fed formula alone) were corrected to concentrations observed in breastfed infants. Taurine supplementation had no effect on the rate of weight gain or on linear growth over the complete course of the study. Thus, taurine supplementation of formulas returns plasma and urine concentrations of this amino acid to those found in human milk-fed infants. However, these data indicate that the supplementation of formulas with taurine has no benefit with respect to growth.

Safety of long-term large doses of aspartame.

Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a randomized, double-blind, placebo-controlled, parallel-group design in 108 male and female volunteers aged 18 to 62 years. Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks. No persistent changes over time were noted in either group in vital signs; body weight; results of standard laboratory tests; fasting blood levels of aspartame's constituent amino acids (aspartic acid and phenylalanine), other amino acids, and methanol; or blood formate levels and 24-hour urinary excretion of formate. There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject. These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day.

Human milk supplementation. Delivery of energy, calcium, phosphorus, magnesium, copper, and zinc.

Human milk when fed to preterm infants is frequently supplemented with human milk fortifiers that provide an additional source of protein, energy, and minerals. Human milk that was provided by the mother of a preterm infant, and that was supplemented with commercially available human milk fortifiers, was assessed under simulated syringe-pump and bolus feeding circumstances for the delivery of energy, calcium, phosphorus, copper, magnesium, and zinc to an infant. In general, the nutrients were not completely delivered with syringe-pump feedings, with the greatest losses occurring in the concentrations of calcium and phosphorus. The losses were more pronounced with the use of a powdered fortifier than with the use of a liquid fortifier. Little or no change in the concentrations of the various nutrients were observed with simulated bolus feeding. We suggest that human milk fortified with supplements be fed with care to assure complete delivery of the nutrients and that infants receiving such feedings be monitored to assure adequate nutritional status.

Protein quantity and quality in term and preterm infants: effects on urine creatinine and expression of amino acid excretion data.

The effect of dietary protein quantity and quality on the excretion of creatinine in preterm and term neonatal infants has been investigated. Whey protein predominant formulas result in increased creatinine excretion as compared with either casein protein predominant formulas or with pooled human milk in preterm infants (p less than 0.001 by ANOVA). The volume of human milk (170 versus 185 versus 200 ml/kg/day) appears to have little effect in these infants. In term infants, few differences among the feeding groups were observed, although creatinine excretion did increase with time. The pattern of creatinine excretion among feeding groups was similar regardless of whether or not the data were expressed in milligrams per deciliter or in milligrams per 24 hours. Small correlations of creatinine excretion with birth weight were observed, but these appeared to vary, depending on the type of feeding. These diet-induced differences in creatinine excretion indicate the need for caution in expressing other urinary metabolites, such as amino acids, relative to creatinine excretion.

Cysteine supplementation of total parenteral nutrition: the effect in beagle pups.

Total parenteral nutrition solutions supplemented with cysteine-HCl (S-TPN, 0.8 mmol/kg/day) were infused into beagle pups from day 10 of life to day 20 (n = 6). Another group of pups received unsupplemented TPN solutions (US-TPN) (n = 6). Fluid, protein, and energy intake from nonprotein sources were similar in both groups. Data from these two groups were compared and similar measurements in normally suckled pups were also compared with the two TPN groups (n = 6). There were significant differences in the rate of weight gain between the pups that received TPN and the pups that were suckled (P less than 0.01). Weight gain, hepatic DNA and protein concentrations, and cerebral DNA and protein concentrations in the pups that received TPN supplemented with cysteine were not different from similar measurements in pups that received unsupplemented TPN. Plasma total cyst(e)ine (Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound) concentrations in the cysteine-supplemented pups (7.9 +/- 1.2 mumol/DL, X +/- SD) were significantly greater than in the unsupplemented pups (4.9 +/- 1.8 mumol/DL). Hepatic glutathione concentrations in the supplemented pups (583 +/- 85 mumol/100 g liver) were also significantly greater than in the unsupplemented pups (392 +/- 113 mumol/100 g liver). These data suggest that the supplementation of TPN solutions with cysteine, even in an animal enzymatically capable of cysteine synthesis, has significant effects on glutathione synthesis.

Role of taurine in feeding the low-birth-weight infant.

Plasma and urinary taurine concentrations, growth, nitrogen balance, duodenal bile salt concentration and pattern, fecal bile acid excretion, and intestinal fat absorption were determined in appropriate for gestational age low-birth-weight infants fed either a whey-predominant cow milk formula or the same formula supplemented with taurine (45 mumol/kg/day). Mean plasma taurine concentration in the two groups did not differ. Mean urinary taurine concentration in the control and supplemented groups over the entire study period were 2.67 +/- 0.69 and 12.41 +/- 5.20 mumol/dl, respectively (P less than 0.05). Urinary taurine concentration in the supplemented infants, however, decreased significantly during the study period. Neither growth nor nitrogen retention differed between the two groups. Mean duodenal concentrations of taurine as well as glycine conjugates of both cholate and chenodeoxycholate were higher in supplemented infants. Total duodenal bile salt concentration correlated positively with taurine status as reflected by urinary taurine excretion (r = 0.71); this correlation plus the lower duodenal cholesterol concentration in supplemented infants suggests that conversion of cholesterol to bile acids was greater in supplemented infants. Mean intestinal fat absorption in control and supplemented infants, however, did not differ.

Total parenteral nutrition in sick preterm infants: effects of cysteine supplementation with nitrogen intakes of 240 and 400 mg/kg/day.

The effects of supplementing total parenteral nutrition (TPN) solutions with cysteine were assessed at two different levels of nitrogen intake by determining nitrogen retention, sulfate excretion, and sulfur-containing amino acid concentrations. Ten infants received 72 mg/kg/day of cysteine-HCl in a TPN solution for a period of 6 days. Five of these infants received 251 +/- 48 (mean +/- SD) mg/kg/day of nitrogen, and five received 403 +/- 45 mg/kg/day of nitrogen. Two other groups of five infants each received unsupplemented TPN at nitrogen intakes of 235 +/- 48 and 412 +/- 54 mg/kg/day, respectively. Fluid and nonprotein caloric intakes were similar for all four groups. Cysteine supplementation increased plasma and urine free cyst(e)ine concentrations and enhanced total sulfur retention, but did not enhance nitrogen retention. [Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound.] Nitrogen retention, sulfate excretion, cyst(e)ine excretion, and plasma taurine concentrations increased as the result of the increase in nitrogen intake.

Feeding the low-birth-weight infant. III. Diet influences bile acid metabolism.

Fasting duodenal bile acid concentrations and conjugation patterns were studied during the first 5 weeks of life in 65 low-birth-weight infants, 31 to 36 weeks of gestational age. One group was fed human milk. Approximately 55% of this milk was pooled, expressed, and pasteurized (62 degrees C for 30 minutes), 35% was similarly treated milk from the infant's own mother, and the remainder (10%) was provided by breast-feeding. The other infants, from 3 days of age, were fed one of three formulas: an adapted formula (F1), F1 supplemented with taurine (F2), or F1 supplemented with taurine and cholesterol (F3). The fasting intraluminal concentration of conjugated bile acids was higher in the infants fed human milk than in the infants fed formulas (F = 30.03, p less than .001) reflecting the higher concentrations of all individual bile acids. No significant increase over time was found in the concentration of total bile acids in any feeding group. Chenodeoxycholic acid concentrations, however, increased significantly over time in the infants fed human milk (r = .286, P less than .05). Thus, in the infants fed human milk, the ratio of cholates to chenodeoxycholates changed from 2.03 to 1.29 (P less than .001), whereas it remained stable (2.61) in the groups fed formula. Tauroconjugated bile acids predominated until at least 5 weeks of life in all the infants fed human milk, F2, or F3. In the infants fed F1, the concentration of glycoconjugates increased and that of tauroconjugates remained stable.(ABSTRACT TRUNCATED AT 250 WORDS)

Feeding the low-birth weight infant: V. Effects of taurine, cholesterol, and human milk on bile acid kinetics.

This study was conducted to compare the influence of diet on the physiologic changes in bile acid kinetics, intraluminal bile acid concentrations, conjugation patterns, and nutrient lipid absorption, which occur postnatally. Preterm infants, 31-35 wk gestation, were fed one of four diets: (a) human milk pasteurized at 62 degrees C for 30 min, 55% from a pooled source, 35% from the infant's own mother, with the remainder (approximately 10%) being fresh human milk; (b) an adapted infant formula (F1); (c) F1 supplemented with taurine, 30 mumol/dl, (F2); and (d) F1 with both taurine, 30 mumol/dl, and cholesterol, 9.6 mg/dl, to a total of 12.7 mg/dl, the levels found in human milk (F3). In all infants, the bile acid pool size increased nearly twofold between 11 and 35 days, irrespective of dietary regimens. Taurine conjugation of bile acids predominated in all infants at 11 days of age and at 35 days in those infants fed human milk or the taurine-supplemented formulas. In taurine-supplemented formulas, the conjugation pattern did not influence bile acid kinetics. However, the bile acid pool and intraluminal bile acid concentrations were significantly greater in infants fed human milk at all ages, suggesting that human milk feeding, per se, uniquely influences intestinal and possibly hepatic function independent of developmental factors.

Preterm infants fed human milk attain intrauterine weight gain.

The adequacy of human milk for low-birth-weight infants remains controversial. In this study, 35 healthy preterm infants with gestational age from 31 to 36 weeks and a birth weight less than 2200 g, were followed until they attained a weight of 2400 g at about 5 to 7 weeks of age. These infants were fed pooled, expressed human milk, partly supplemented with their own mother's milk, at intakes of 185 and 200 ml/kg/day. There were no consistent differences between the feeding groups in the rate of gain in weight, length, or head circumference, in serum total protein, in acid-base status, or in plasma amino acid concentrations. It is concluded that pooled, expressed human milk in volumes of 185 or 200 ml/kg/day produces a postnatal weight gain (196 +/- 6 or 205 +/- 7 g/week, respectively) in healthy preterm infants with a gestational age over 31 weeks which compares to intrauterine weight gain (207 g/week). This growth is achieved without apparent metabolic stress.

Feeding the low-birth-weight infant: I. Taurine and cholesterol supplementation of formula does not affect growth and metabolism.

Taurine and cholesterol are constituents of human milk that are present in smaller amounts in infant formulas. Infants fed such formulas have lower plasma and urine concentrations of taurine and of serum total cholesterol. In the present investigation, in infants of 31 to 36 weeks gestational age, the effects of supplementing a 1.5 g/100 mL whey-predominant formula with taurine alone or with taurine plus cholesterol were examined. Infants fed the supplemented formula were compared with infants fed the unsupplemented formula and with infants fed pooled, expressed human milk (185 mL/kg/d). Approximately 45% of the human milk provided to each infant was that of the infant's mother (35% pasteurized and 10% fresh). From the time of reaching a weight of 2,400 g to 4 months of age the last group of infants was fed ad libitum. No consistent statistically significant differences in growth, as measured by rate of gain in crown-rump length, crown-heel length, or head circumference, were observed. There was a tendency, however, for the formula-fed infants to gain weight more slowly before reaching 2,400 g and to gain weight more quickly after a weight of 2,400 g was attained to 4 months of age. No differences in concentrations of BUN, total serum proteins, or acid-base status were observed among the formula-fed groups. The concentration of BUN increased in the formula-fed groups compared with the group fed human milk during the last half of the study. The formula-fed infants tended to have higher total serum proteins and to be slightly more acidotic than the infants fed human milk prior to discharge at a weight of 2,400 g but not thereafter. Thus, infants fed 185 mL/kg/d gained weight at rates comparable to those for fetuses of the same gestational age. Supplementation of formulas with taurine or taurine plus cholesterol did not produce changes in growth or general metabolism discernible under the present experimental conditions.

Feeding the low-birth-weight infant: II. Effects of taurine and cholesterol supplementation on amino acids and cholesterol.

Plasma and urine concentrations of taurine were consistently lower in preterm infants fed unsupplemented formula than those observed in the infants fed human milk or formulas supplemented with taurine alone or with taurine plus cholesterol. Such supplementation of formula restored plasma and urine concentrations of taurine to those observed in the infants fed human milk. Taurine was the only amino acid that was present at lower concentrations in the infants fed unsupplemented formula than in those fed human milk. The other acidic and neutral amino acids were present in higher concentrations in the formula-fed infants than in the group fed human milk either during the early weeks of the study (serine, glutamine, glycine, alanine, tyrosine, and methionine) or consistently higher during the entire study (threonine, glutamate, citrulline, valine, isoleucine, leucine, and phenylalanine). Supplementation of formula with taurine plus cholesterol did not appear to have any effect on the amino acid concentrations in the plasma and urine, other than that on taurine itself. Plasma total cholesterol concentration decreased during the fifth to the 12th postnatal weeks of life in all feeding groups. It then returned to the concentrations found during the first and third postnatal weeks in all feeding groups except in the infants fed formulas supplemented with taurine plus cholesterol which had a greater decrease.

Cyst(e)ine measurements during total parenteral nutrition.

Using a method that measures plasma protein-bound 1/2 cystine, plasma free cyst(e)ine, and urine free cyst(e)ine, we have observed that infants receiving total parenteral nutrition supplemented with cysteine-HCl have significantly higher plasma and urine free cyst(e)ine concentrations (11.3 +/- 3.4 microns/dl and 47.2 +/- 24.0 microns/dl, means +/- SD) than when 1/2 cystine concentrations are measured by automated amino acid analysis (7.4 +/- 2.0 microns/dl, plasma and 25.0 +/- 7.0 microns/dl, urine). These data suggest that both the sulfhydryl and disulfide form of cyst(e)ine must be measured to assess the effect of cysteine-HCl supplemented total parenteral nutrition.

Taurine and other free amino acids in milk of man and other mammals.

Taurine and other free amino acids have been determined in human milk of a number of other species. Taurine is the most abundant free amino acid in the milk of the gerbil, mouse, cat, dog and rhesus monkey. Taurine is the second most abundant amino acid in the milk of the rat, baboon, chimpanzee, sheep, Java monkey and man. Taurine is not a major constituent in the milk of the guinea pig, rabbit, cow and horse. The milk of each species has a characteristic free amino acid pattern which may be an indication of the relative nutritional importance of these compounds during early postnatal development.

Milk protein quantity and quality in low-birth-weight infants: II. Effects on selected aliphatic amino acids in plasma and urine.

The optimal quantity and quality of protein for low-birth-weight infants is undefined. In this study, 106 well, appropriate-for-gestational-age, low-birth-weight infants weighing 2,100 gm or less were divided into three gestational age groups and assigned randomly within each age group to one of five feeding regimens: pooled human milk; formula 1 (protein content, 1.5 gm/100 ml- 60 parts bovine whey proteins to 40 parts bovine caseins); formula 2 (3.0 gm/100 ml, 60:40); formula 3 (1.5 gm/100 ml, 18:82); and formula 4 (3.0 gm/100 ml, 18:82). The concentrations of the free amino aicds in the plasma and urine of these infants were determined. The plasma concentrations of free amino acids were generally far greater in the infants fed the 3.0-gm/100 ml protein diets than they were in the infants fed pooled human milk. The plasma concentrations of free amino acids of the infants fed the 1.5-gm/100 ml protein diets were intermediate. In general, the concentrations of the free amino acids in the plasma of the infants fed the 3.0-gm/100 ml casein-predominant formula (F4) were furthest from those fed pooled human milk. Glutamate showed the highest plasma amino acid concentrations in infants fed the 3.0-gm/100 ml casein-predominant formula (F4) were furthest from those fed pooled human milk. Glutamate showed the highest plasma amino acid concentrations in infants fed both the high- and low-protein casein-predominant formulas. This was true despite the fact that the intake of glutamate on the high-protein, whey-predominant formula was twice that on the low-protein, casein-predominant formula. The differences between groups in the essential amino acids in plasma were generally greater than those of the nonessential amino acids. The concentrations of amino acids in the urine tended to parallel those of the plasma.

Milk protein quantity and quality in low-birth-weight infants. III. Effects on sulfur amino acids in plasma and urine.

Well, appropriate-for-gestational age, low-birth-weight infants weighing 2,100 gm or less were divided into three gestational age groups and assigned randomly within each age group to one of five feeding regimens: pooled human milk; formula 1 (F1) = 1.5gm/dl protein, 60 parts bovine whey proteins: 40 parts bovine caseins; F2 = 3.0 gm/dl, 60:40; F3 = 1.5 gm/dl, 18:82; F4=3.0 gm/dl, 18:82. Plasma and urine concentrations of methionine and of cystathionine were higher in the infants fed F1 to F4 than in the infants fed BM. The plasma cystine concentrations of infants fed F2 (which had a cystine content at least twice that of any of the other formulas) were significantly higher than those of infants fed BM. Plasma taurine concentrations of infants fed F1 or F4, which were virtually devoid of taurine, decreased steadily during the course of study becoming lower than those of infants fed BM. Urine taurine concentrations of infants fed F1, F3, or F4 (but not F2 which had more taurine than F1, F3, or F4) were lower than those of infants fed BM. These results provide further evidence for the limited capacity of the preterm human infant to convert methionine to cystine, owing to delayed maturation of cytathionase, and suggest a limited capacity to convert cystine to taurine. The latter suggestion is consistent with low human hepatic cysteinesulfinic acid decarboxylase activity 0.26 (fetal) and 0.32 (adult) nmoles/mg protein/hour vs 468 in rat liver.