Lysine kinetics in preterm infants: the importance of enteral feeding.(Small Intestine)

Gut 2004;53:38-43

Introduction: Lysine is the first limiting essential amino acid in the diet of newborns. First pass metabolism by the intestine of dietary lysine has a direct effect on systemic availability. We investigated whether first pass lysine metabolism in the intestine is high in preterm infants, particularly at a low enteral intake.

Patients and methods: Six preterm infants (birth weight 0.9 (0.1) kg) were studied during two different periods: period A (n = 6): 40% of intake administered enterally, 60% parenterally; lysine intake 92 (6) [micro]mol/(kgXh); and period B (n = 4): 100% enteral feeding; lysine intake 100 (3) [micro]mol/(kgXh). Dual stable isotope tracer techniques were used to assess splanchnic and whole body lysine kinetics.

Results: Fractional first pass lysine uptake by the intestine was significantly higher during partial enteral feeding (period A 32 (10)% v period B 18 (7)%; p<0.05). Absolute uptake was not significantly different. Whole body lysine oxidation was significantly decreased during full enteral feeding (period A 44 (9) v period B 17 (3) [micro]mol/(kgXh); p<0.05) so that whole body lysine balance was significantly higher during full enteral feeding (period A 52 (25) v period B 83 (3) [micro]mol/(kgXh); p<0.05).

Conclusions: Fractional first pass lysine uptake was much higher during partial enteral feeding. Preterm infants receiving full enteral feeding have lower whole body lysine oxidation, resulting in a higher net lysine balance, compared with preterm infants receiving partial enteral feeding. Hence parenterally administered lysine is not as effective as dietary lysine in promoting protein deposition in preterm infants.

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The primed constant intravenous infusion of amino acids labelled with stable isotopes has become the reference method for studying whole body protein dynamics. (1-3) By measuring oxidation rates of specific amino acids directly, conclusions can be drawn on the excessive supply of a particular amino acid. Because of limitations in studying nutrient metabolism in preterm neonates, several studies in neonatal animals have been performed to quantify protein metabolism in vivo. These studies have shown that the portal drained viscera (intestines, pancreas, spleen, and stomach) utilise more than 50% of dietary protein intake for protein synthesis and biosynthetic pathways, (4-7) and is a major site of lysine oxidation. (8) Of particular importance is the utilisation rate by the intestine of essential amino acids. A high utilisation rate of essential amino acids by the intestine results in lower systemic availability of essential amino acids. We were specifically interested in lysine, which is the first limiting amino acid in milk fed mammalian newborns. (9) Thus if the amount of protein in the diet is not adequate, the rate of protein synthesis and growth will be determined by the amount of lysine.

The neonatal piglet is generally considered to be a good model for the human infant with respect to rate and pattern of gastrointestinal tract development. (10) In addition, amino acid patterns are similar between piglets and infants in terms of both plasma concentrations and requirements. (11 12) However, there are no data on lysine kinetics in infants while in adults splanchnic lysine uptake has been found to vary between 5% and 35% of lysine intake. (7 13)

Largely as a result of their immature gastrointestinal tract, all preterm infants face a period of compromised enteral intake in their first weeks of life, and they frequently receive a combined parenteral and enteral nutrient supply. Based on our finding that absolute lysine utilisation by the intestine of neonatal pigs appears to be independent of lysine intake, (8) we postulated that fractional first pass lysine utilisation would be much higher during a restricted enteral intake. Importantly, this would result in a lower systemic availability of dietary lysine. Therefore, we measured first pass lysine uptake in response to two different enteral intakes in neonates.

Apart from first pass lysine utilisation, the magnitude of intestinal lysine catabolism is also important to the nutrition of preterm newborns. The energy needed to sustain the high rate of protein turnover in the gut is largely derived from oxidation of non-essential amino acids. (4 14) However, some essential amino acids, including lysine, are also oxidised, which leads to irreversible loss. (8 15 16) Despite the general belief that the intestinal mucosa does not possess lysine catabolic enzymes, (17 18) we showed that intestinal oxidation of dietary lysine in pigs accounted for approximately 30% of whole body lysine oxidation. (6) Whether dietary lysine is oxidised by splanchnic tissues in humans has not yet been investigated. Quantification of the response of splanchnic and whole body lysine oxidation on the level of enteral protein intake in preterm infants was the second objective of this study.

METHODS

Patients

The study protocol was approved by the Erasmus University Institutional Review Board. Written informed consent was obtained from parents. Splanchnic and whole body lysine kinetics were quantified in preterm infants during partial enteral feeding (period A) and full enteral feeding (period B). Patients eligible for this study were premature infants with a birth weight ranging from 750 g to 1250 g who were appropriate for gestational age according to the charts of Usher and McLean. (19) Excluded from the study were infants who had congenital anomalies, or gastrointestinal or liver diseases. …