To assess the response of protein turnover to graded levels of amino acid (AA) intakes, leucine kinetics were determined in six 8- to 16-yr-old patients in a stable nutritional status receiving home parenteral nutrition (PN) for short-bowel syndrome or intestinal pseudo-obstruction syndrome. Although daily energy intake was kept constant at 68.7 +/- 13 kcal/kg lean body mass (LBM) with 25.4 +/- 3.6% lipid, patients were given, for three consecutive 7-day periods, 0.7, 1.5, or 2.5 g AA.kg LBM-1.day-1, with the order of the regimens being randomized. On day 7 of each period, a 4-h infusion of L-[1-13C]leucine was performed during intravenous feeding; plasma [13C]ketoisocaproate and expired 13CO2 enrichments were used to assess whole body leucine turnover (Ra), oxidation rate (Ox), nonoxidative disposal [an estimate of protein synthesis (S)], and leucine derived from protein breakdown (B). Urine collection (24 h) was performed for determination of nitrogen excretion. Results indicate a dose-dependent rise in plasma leucine concentration, Ra, and Ox but no significant change in B. There was a significant increase of S (P = 0.04 analysis of variance) with increased AA intakes as well as net leucine balance (P = 0.02). Results are consistent with improved leucine balance, when leucine intake increases, despite increased leucine oxidation. The net protein gain observed with higher AA intakes may suggest a beneficial effect for children receiving long-term PN.
We evaluated the effect of ornithine ketoglutarate (OKG) in reversing abnormal growth in six prepubertal children receiving total parenteral nutrition (TPN) for 5-10 y. They were 1-4 SDs below their expected 50th percentile for height. The energy and nitrogen intakes were unchanged from 8 mo before the beginning of the study until its completion. Two consecutive periods of 5 mo each were studied. OKG (15 g) was added to the parenteral solution during the first period (OKG+) but not during the second period (OKG-). Height velocity (HV) increased (P < 0.05) from a median of 3.8 cm/y to 6.45 cm/y (range 1.8-6.7) during the OKG+ period, and decreased (P < 0.05) to a median of 3.65 cm/y in the OKG- period. Plasma concentrations of insulin-like growth factor 1 (IGF1), glutamine, and glutamate increased (P < 0.05) during the OKG+ period. Variations of IGF1 concentrations correlated with HV variations (r = 0.82, P < 0.005) during both periods. This study demonstrates that OKG is associated with statural growth acceleration and increased IGF1 concentrations.
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