Acute Effects of Intravenous Glutamine Supplementation on Protein Metabolism in Very Low Birth Weight Infants: A Stable Isotope Study

Abstract

Although very low birth weight infants are subjected to severe stress and glutamine is now considered a conditionally essential amino acid that may attenuate stress-induced protein wasting in adults, current amino acid solutions designed for neonatal parenteral nutrition do not contain glutamine. To determine whether a short-term supplementation with i.v. glutamine would affect protein metabolism in very low birth weight infants, 13 preterm neonates (gestational age, 28 -30 wk; birth weight, 820 -1610 g) receiving parenteral nutrition supplying 1.5 g · kg Ϫ1 · d Ϫ1 amino acids and approximately 60 nonprotein kcal · kg Ϫ1 · d Ϫ1 were randomized to receive an i.v. supplement made of either 1) natural L-glutamine (0.5 g · kg Ϫ1 · d Ϫ1 ; glutamine group), or 2) an isonitrogenous glutamine-free amino acid mixture (control group), for 24 h starting on the third day of life. On the fourth day of life, they received a 2-h infusion of NaH 13 CO 3 to assess the recovery of 13 C in breath, immediately followed by a 3-h L-[1-13 C]leucine infusion. Plasma ammonia did not differ between the groups. Glutamine supplementation was associated with 1) higher plasma glutamine (629 Ϯ 94 versus 503 Ϯ 83 M, mean Ϯ SD; p Ͻ 0.05, one-tailed unpaired t test), 2) lower rates of leucine release from protein breakdown (Ϫ16%, p Ͻ 0.05) and leucine oxidation (Ϫ35%, p Ͻ 0.05), 3) a lower rate of nonoxidative leucine disposal, an index of protein synthesis (Ϫ20%, p Ͻ 0.05), and 4) no change in protein balance (nonoxidative leucine disposal Ϫ leucine release from protein breakdown, NS). We conclude that although parenteral glutamine failed to enhance rates of protein synthesis, glutamine may have an acute protein-sparing effect, as it suppressed leucine oxidation and protein breakdown, in parenterally fed very low birth weight infants. During the last decade, several clinical trials have produced compelling evidence for a role of glutamine in improving nitrogen balance in adult patients undergoing elective gastrointestinal surgery (1, 2), cholecystectomy (3), or bone marrow transplantation (4). Other studies suggested glutamine might exert a trophic effect on gut as well (5-7).Although preterm infants are exposed to stress-induced protein wasting and intestinal frailty, conventional amino acid solutions designed for neonatal i.v. nutrition do not contain glutamine, because glutamine is classified as nonessential, has relatively poor solubility, and cannot be heat sterilized. Yet Neu et al. (8)

Suplementação enteral e parenteral com glutamina em neonatos pré-termo e com baixo peso ao nascer

“…A glutamina estimula a síntese e inibe a degradação protéica, o que poderia contribuir para a obtenção de um balanço protéico muscular menos negativo em situações catabólicas (Hammarqvist et al, 1989;Millward, Jepson, Omer, 1989). Em neonatos PT e com BPN, o efeito da suplementação parenteral com glutamina no metabolismo protéico foi avaliado por dois estudos (Des Robert et al, 2002;Kalhan et al, 2005), nos quais os bebês foram aleatoriamente selecionados para receber suplementação com glutamina intravenosa ou uma mistura de aminoácidos isonitrogenada isenta de glutamina. No protocolo utilizado por Des Robert et al (2002), utilizou-se a suplementação aguda (24 horas) com 0,5 g de glutamina/kg/dia em neonatos PT e com BPN com quatro dias de vida.…”

“…Em neonatos PT e com BPN, o efeito da suplementação parenteral com glutamina no metabolismo protéico foi avaliado por dois estudos (Des Robert et al, 2002;Kalhan et al, 2005), nos quais os bebês foram aleatoriamente selecionados para receber suplementação com glutamina intravenosa ou uma mistura de aminoácidos isonitrogenada isenta de glutamina. No protocolo utilizado por Des Robert et al (2002), utilizou-se a suplementação aguda (24 horas) com 0,5 g de glutamina/kg/dia em neonatos PT e com BPN com quatro dias de vida. O grupo suplementado apresentou maior concentração plasmática de glutamina e menor degradação protéica e oxidação de leucina, entretanto, não foi observada melhora no balanço protéico em resposta à suplementação (Tabela I).…”

“…Corroborando os resultados de Des Robert et al (2002), no estudo de Kalhan et al (2005) foi constatada diminuição da degradação protéica, concomitantemente à redução da sín-tese de novo de glutamina, em resposta à suplementação, o que sugere efeito inibitório da glutamina exógena sobre sua síntese. Por outro lado, não foi observada diferença na concentração plasmática de glutamina entre os grupos.…”

Amino Acids, Glutamine, and Protein Metabolism in Very Low Birth Weight Infants

“…A third group of babies received amino acids 1.5 g/kg/d for 20 h followed by 3.0 g/kg/d for 20 h (AA-Ext). Glutamine and protein/nitrogen kinetics were examined using [5][6][7][8][9][10][11][12][13][14][15] 5 h (AA1.5) resulted in decrease in rate of appearance (Ra) of phenylalanine and urea, but had no effect on glutamine Ra. Infusion of amino acids at 3.0 g/kg/d for 20 h resulted in increase in DGln, leucine transamination, and urea synthesis, but had no effect on Ra phenylalanine (AA-Ext).…”

“…Because the concentration of plasma glutamine is lower in VLBW infants, and the currently used parenteral nutrient solutions do not contain glutamine, VLBW premature infants were identified as another group of subjects who could potentially benefit from supplementation of enteral and parenteral nutrition with glutamine (7)(8)(9). However, whether provision of a higher amount of parenteral amino acids to these VLBW infants enhances the rate of DGln has not been examined.…”