Michael C. Storm

Effect of Intravenous L-Carnitine on Growth Parameters and Fat Metabolism during Parenteral Nutrition in Neonates

To determine whether intravenous carnitine can improve nutritional indices, neonates requiring parenteral nutrition were randomized into carnitine treatment (n = 23) and control (n = 20) groups. Observed plasma lipid indices, carnitine and nitrogen balances, and plasma carnitine concentrations were not different in the prestudy period. Under standardized, steady-state conditions, 0.5 g/kg Intralipid was administered intravenously over 2 hr prior to carnitine administration, after infants received 7 days of 50 mumol/kg/day, and after a second 7 days of 100 mumol/kg/day of continuous intravenous L-carnitine as part of parenteral nutrition. Triglyceride (TGY), free fatty acid (FFA), acetoacetate (AA), beta-hydroxybutyrate (BOB), and plasma carnitine concentrations were measured prior to and at 2, 4, and 6 hr after the initiation of the lipid bolus. Twenty-four-hour urine collections for nitrogen and carnitine balance were obtained on days 7 and 14. Neonates receiving carnitine had significantly greater concentrations of plasma carnitine on days 7 and 14 (p less than 0.001). Greater nitrogen (p less than 0.05) and carnitine (p less than 0.001) balances and weight gain (week 2, p less than 0.05) were found in the carnitine-supplemented group when compared with controls. On day 14, (BOB + AA)/FFA ratios were significantly higher (p less than 0.05), and peak TGY concentrations and 6-hr FFA concentrations were significantly lower (p less than 0.05) in the treatment group. Carnitine supplementation was associated with modest increases in growth and nitrogen accretion possibly by enhancing the neonates ability to utilize exogenous fat for energy.

Supplemental Alanylglutamine, Organ Growth, and Nitrogen Metabolism in Neonatal Pigs Fed by Total Parenteral Nutrition

The objective of this study was to determine whether supplemental glutamine (alanylglutamine dipeptide) is effective in preventing small intestinal mucosal atrophy associated with total parenteral nutrition and whether it affects the growth of other organs in neonatal pigs. We compared organ growth, intestinal enzyme activity, and plasma nitrogen metabolites in 4-day-old pigs randomly selected to receive total parenteral nutrition supplemented with 0 g, 2.0 g, or 4.5 g of glutamine per deciliter for a total amino acid intake of either 11 or 25 g.kg-1.d-1 for 7 days. Glutamine supplementation increased (60% to 100%) plasma concentrations of glutamine, urea nitrogen, ammonia, and both jejunal villus height and surface area, but it did not significantly affect jejunal mucosal protein and DNA masses or the relative growth of liver, kidneys, and brain. No histologic evidence of tissue toxicity was found. Supplementing large amounts of glutamine (alanylglutamine dipeptide) did not completely prevent total parenteral nutrition-associated intestinal mucosal atrophy but did improve villus morphology without affecting vital organ growth or histology.

Glutamine or Glutamic Acid Effects on Intestinal Growth and Disaccharidase Activity in Infant Piglets Receiving Total Parenteral Nutrition

This study was designed to measure the effect of free glutamine or glutamic acid supplementation on small intestinal growth and disaccharidase enzyme activity in 7-day-old miniature piglets. The piglets received one of three total parenteral nutrition solutions exclusively for 7 days. All three solutions were isonitrogenous and isocaloric, and glutamine or glutamic acid was included at physiological levels (5% of the total amino acid content) in two of the three solutions; the third (control) contained neither glutamine nor glutamic acid. No differences were seen between groups in plasma glutamine or glutamic acid concentrations. Similarly, no effect was observed on small intestinal protein or DNA content or on the specific activities of lactase, sucrase, or maltase. These data demonstrate that in the healthy miniature piglet, parenteral glutamine or glutamic acid supplemented at physiological doses does not influence small intestinal growth and development.

Oral glutamine supplementation decreases resting energy expenditure in children and adolescents with sickle cell anemia.

Objectives:To determine the effects of orally administered glutamine on the resting energy expenditure (REE) and nutritional status of children and adolescents with sickle cell anemia. Methods:Twenty-seven children and adolescents (13 boys, 14 girls), 5.2 to 17.9 years old (median 11.0 years), received orally administered glutamine (600 mg/kg per day) for 24 weeks. Measures of REE and other nutritional parameters were compared at baseline and 24 weeks. Results:After 24 weeks, the patients’ median REE (kcal/d) decreased by 6% (P = 0.053) as indicated by the Harris Benedict equations and by 5% (P = 0.049) as indicated by the modified equations. Patients with less than 90% ideal body weight had even greater declines in REE after 24 weeks (P < 0.03 and 0.02, respectively). Improvements in nutrition parameters and in two amino acids in the plasma were observed. Conclusions:After 24 weeks of orally administered glutamine, children and adolescents with sickle cell anemia had a decrease in REE and improvement in nutritional parameters. Those who were underweight had a greater decrease in REE than those of normal body weight. Lowering REE may be an effective way to improve the growth of these children and adolescents.

Cysteine supplementation results in normalization of plasma taurine concentrations in children receiving home parenteral nutrition

We evaluated plasma sulfur amino acid concentrations in children with short gut syndrome receiving home parenteral nutrition (n = 6). Cysteine HCl addition to solutions formulated with a pediatric amino acid product will increase plasma taurine concentrations to within the normal reference range.

Adequacy of sulfur amino acid intake in infants receiving parenteral nutrition

Taurine and cysteine are considered essential nutrients for the infant receiving parenteral nutrition (PN). To define the adequacy of sulfur amino acid content in a pediatric amino acid formulation, evaluation of urinary excretion, fractional excretion, and balance studies for taurine, total (free + bound) cyst(e)ine (cysteine + cystine), and methionine were completed under steady-state conditions of energy and protein intake in 18 preterm infants receiving PN. These infants had a mean gestational age of 34.5 ± 2.4 weeks, postnatal age of 19 ± 18 days, weighed 2.1 ± 0.5 kg, and received 100 ± 22 kcal/kg/day and 2.8 ± 0.1 g/kg/day of amino acids. Plasma concentrations for the sulfur-containing amino acids were within the reference range; however, the excretion and fractional excretion of taurine (3.7 ± 7.8 mg/kg/day, 17 ± 15%) and cyst(e)ine (12.0 ± 7.1 mg/kg/day, 33 ±19%) were at the upper limits of normal reported experience. Methionine excretion (0.9 ± 1.0 mg/kg/day) and fractional excretion (16 ± 22%) were within normal reported experience. For taurine, fractional excretion inversely correlated with weight at the time of study ( r = −0.59, P

Plasma carnitine concentration and lipid metabolism in infants receiving parenteral nutrition

The relationships among plasma total carnitine concentration, postnatal age, and fatty acid metabolism were evaluated in 57 infants receiving parenteral nutrition. Concentrations of plasma carnitine, triglycerides, free fatty acids, acetoacetate, and beta-hydroxybutyrate were determined before and at 2 and 4 hours from the beginning of a standardized 2-hour lipid infusion. Plasma carnitine concentrations declined with increasing postnatal age. There were no significant differences in gestational age or triglyceride concentrations between infants less than or equal to 4 weeks of age and those greater than 4 weeks of age, whereas free fatty acid concentrations were lower and acetoacetate and beta-hydroxybutyrate concentrations were higher in the younger infants. Infants less than or equal to 4 weeks of age were further grouped according to plasma carnitine concentration greater than 13 nmol/ml (group 1) and less than or equal to 13 nmol/ml (group 2) and were then compared with infants greater than 4 weeks of age (group 3). There were no significant differences in triglyceride concentrations among the three groups; free fatty acids, acetoacetate, and beta-hydroxybutyrate concentrations for group 2 patients were similar to those of group 1 patients or fell between values for group 1 and group 3 patients. These results demonstrate decreasing plasma carnitine concentrations and possibly for more than 4 weeks.

Relative bioavailability of carnitine supplementation in premature neonates

BACKGROUND Carnitine is an important nutrient in the infant diet. We compared total plasma carnitine concentrations in premature neonates supplemented with carnitine via parenteral and enteral nutrition. METHODS This is a post hoc analysis of plasma total carnitine concentrations and carnitine intake in neonates randomized in a previous study to receive 20 mg/kg/d carnitine supplementation over 8 weeks. Neonates received l-carnitine initially via parenteral nutrition (PN). When neonates were fed enterally, oral supplementation of l-carnitine was given in divided doses with each feeding. RESULTS Sixteen neonates (27 +/- 2 weeks gestation; 2.9 +/- 1.0 days postnatal age at enrollment; 965.6 +/- 279.1 g birth weight) are included. Concentrations were below reference range (31.1-60.5 nmol/mL) at baseline and exceeded reference range from week 1 through the last study period. Concentrations were not different from week 1 (108 +/- 49) through weeks 4 (87 +/- 34) and 8 (83 +/- 31). Carnitine intakes and concentrations were compared in neonates receiving 100% parenteral carnitine at week 1 (n = 6) and 100% enteral carnitine at week 8 (n = 8). Concentrations at week 1 (100.1 +/- 27.9) were not different (p = .19) from week 8 (78.6 +/- 29.3); an estimate of relative bioavailability was 78.6%. Bioavailability with paired analysis of neonates (n = 5) receiving 100% parenteral carnitine at week 1 and 100% enteral carnitine at week 8 was 83.7% +/- 41.2% (30.1%-140.6%). CONCLUSIONS Parenteral and enteral supplementation of 20 mg/kg/d carnitine results in plasma total carnitine concentrations that exceed the reference range. Concentrations are not different between parenteral to enteral supplementation, suggesting that enteral carnitine is well absorbed when given daily in divided doses with enteral feedings.

Sulfur amino acid metabolism in infants on parenteral nutrition

In the infant on parenteral nutrition, cysteine supplementation has been suggested due to low levels of hepatic cystathionase activity limiting synthesis from methionine. We have examined the plasma concentrations of sulfur amino acids in four groups of post-surgical infants requiring parenteral nutrition receiving (A) a low methionine + cysteine + taurine formula, (B) a high methionine formula (non-steady state), (C) a high methionine formula (steady state), and (D) a high methionine + cysteine formula. Plasma methionine concentrations were above the normal reference range (2.2-4.9 micromol/dL) of normal breast-fed infants in Groups B (15.9 +/- 10.7 micromol/dL) and D (5.7 +/- 1.9 micromol/dL) and at the upper limit for Group C (4.9 +/- 1.7 micromol/dL). Total cysteine/cystine concentrations (normal reference range, 10.2-20.4 micromol/dL) were highest in Groups A (18.9 +/- 3.5 micromol/dL) and D (16.8 +/- 5.3 micromol/dL) that received cysteine HCI supplementation, and lowest in Group B (8.6 +/- 3.7 micromol/dL) that received no cysteine in non-steady state. All plasma free cystine concentrations were below the normal reference range (3.6-6.8 micromol/dL). Plasma taurine concentrations were not significantly different among the four groups and all were within the normal reference range (0.6-16.2 micromol/dL). The strikingly elevated methionine and low total cysteine/cystine values in Group B suggested the existence of a feedback loop of methionine conversion below the level of homocysteine. Equilibrium of methionine and cysteine/cystine plasma concentrations did occur, in time. Parenteral cysteine administration resulted in a greater proportion of plasma free cysteine concentration, but not cystine. The proportion of free to bound cysteine/cystine, as well as the proportion of free cystine to cysteine, was not normal during parenteral nutrition with or without cysteine HCI supplementation. Little benefit in plasma concentrations was derived from cysteine HCI supplementation to a high methionine formulation.

Urinary Nitrogen Constituents in the Postsurgical Preterm Neonate Receiving Parenteral Nutrition

Minimal information is available defining urinary nitrogen constituents in preterm neonates receiving parenteral nutrition (PN). The study objective was to evaluate 24-hour urine collections for total urinary nitrogen (TUN), urinary urea nitrogen (UUN), and the nitrogen content in creatinine, ammonia, free amino acids, protein, hippuric acid, and uric acid at baseline (days 1 to 2 of PN and days 1 to 3 after surgery) and 7 days later in eight preterm, postsurgical neonates. Calculation of undetermined nitrogen was also completed. Comparisons with historic, normal data were made for each urinary nitrogen constituent. At baseline, PN provided 59 +/- 10 nonprotein kcal/kg.day-1 and 430 +/- 54 mg/kg.day-1. At day 7, PN provided 106 +/- 23 nonprotein kcal/kg.day-1 and 432 +/- 30 mg/kg.day-1. TUN, UUN, and protein nitrogen decreased significantly from baseline at day 7 (p < .05). The percentages of TUN as amino acids, creatinine, and uric acid nitrogen were calculated. Percent amino acid nitrogen (6.0 +/- 2.3% vs 8.4 +/- 1.5%, p < .05), percent creatinine nitrogen (1.6 +/- 0.5% vs 2.9 +/- 0.8%, p < .001) and percent uric acid nitrogen (1.7 +/- 0.9% vs 3.6 +/- 2.1%, p < .05) increased significantly at day 7. The observed urinary free amino acid nitrogen fraction represented a higher percentage of TUN both at baseline and at day 7 when compared with term neonatal reference data, whereas creatinine nitrogen, uric acid nitrogen, and protein nitrogen represented a lower percentage of TUN. However, amino acid and creatinine nitrogen as a percentage of TUN were similar to levels in milk formula-fed preterm infants.(ABSTRACT TRUNCATED AT 250 WORDS)