Increasing plasma glutamine in postoperative patients fed an arginine-rich immune-enhancing diet-A pharmacokinetic randomized controlled study

Objective. Immune-enhancing diets (IEDs) rich in arginine (ARG) reduce morbi-mortality In trauma and surgical patients. Among the pharmaconutrients inducing these effects, ARG may be involved by generating active metabolites such as glutamine (GLN). However, the ability of an ARG-endched diet to normalize GLN plasma levels In Intensive care unit (ICU) patients has never been documented. To analyze plasma GLN and related amino acid (AA) kinetics in response to an ARG-enriched IED In ICU surgical patients. Design: This prospective, randomized, single-blind, comparative study was performed on 22 patients randomized to receive total enteral nutrition for 7 days with either an ARG-enriched IED or a standard formula (rendered isonitrogenous to the IED, S group, n = 11), providing 30 kcal/kg/day and 0.3 g N/kg/day. Measurements. Plasma AA concentrations were measured on day 5 after a 3-hour washout period (basal values = T-0) and after 30, 60, 90, 120, 180, and 360 minutes of enteral nutrition. The primary end point was the variation In plasma GLN from T-0 to T-00. Results: Only the IED-fed patients showed an increase in plasma levels of GLN (differences [T-00 - T-0]: +40 +/- 6 vs. -35 +/- 18 mu mol/L, mean +/- SEM, P < 0.05, two-way analysis of variance), ARG (+35 +/- 5 vs.+1 +/- 4 mu mol/L, p < 0.05), ornithine (+23 +/- 6 vs. - 2 +/- 2 mu mol/L, p < 0.05), and proline (+ 36 +/- 10 vs. -6 +/- 11 mu mol/L, p < 0.05). Conclusion: To our knowledge, this Is the first reported pharmacokinetic study on an IED even though these products have been on the market for 20 years. Our main result Is that administering an ARG-enriched IED causes a significant increase in plasma GLN probably from do novo GLN synthesis from ARG. This suggests that the ARG present in IED can serve to supply GLN to ICU patients, who are usually depleted in this conditionally essential AA during injury. (Crit Care Med 2009; 37:501-509)