A pilot study of a non-invasive oral nitrate stable isotopic method suggests that arginine and citrulline supplementation increases whole-body NO production in Tanzanian children with sickle cell disease

作者：Marealle Alphonce I; Siervo Mario; Wassel Sara; Bluck Les; Prentice Andrew M; Minzi Omary; Sasi Philip; Kamuhabwa Appolinary; Soka Deogratias; Makani Julie; Cox Sharon E^*

来源：Nitric Oxide-Biology and Chemistry, 2018, 74: 19-22.

DOI：10.1016/j.niox.2017.12.009

Background: Low bioavailability of nitric oxide (NO) is implicated in the pathophysiology of sickle cell disease (SCD). We designed a nested pilot study to be conducted within a clinical trial testing the effects of a daily ready to-use supplementary food (RUSF) fortified with arginine (Arg) and citrulline (Citr) vs. non-fortified RUSF in children with SCD. The pilot study evaluated 1) the feasibility of a non-invasive stable isotope method to measure whole-body NO production and 2) whether Arg+Citr supplementation was associated with increased whole-body NO production. Subjects: Twenty-nine children (70% male, 9-11years, weight 16.3-31.3 kg) with SCD.
Methods: Sixteen children received RUSF + Arg/Citr (Arg, 0.2 g/kg/day; Citr, 0.1 g/kg/day) in combination with daily chloroquine (50 mg) and thirteen received the base RUSF in combination with weekly chloroquine (150 mg). Plasma amino acids were assessed using ion-exchange elution (Biochrom-30, Biochrom, UK) and whole-body NO production was measured using a non-invasive stable isotopic method.
Results: The RUSF+Arg/Citr intervention increased plasma arginine (P = .02) and ornithine (P = .003) and decreased the ratio of asymmetric dimethylarginine to arginine (P = .01), compared to the base RUSF. A significant increase in whole-body NO production was observed in the RUSF-Arg/Citr group compared to baseline (weight-adjusted systemic NO synthesis 3.38 +/- 2.29 mu mol/kg/hr vs 2.35 +/- 1.13 mu mol/kg/hr, P = .04). No significant changes were detected in the base RUSF group (weight-adjusted systemic NO synthesis 2.64 +/- 1.14 mu molAcg/hr vs 2.53 +/- 1.12 mu mol/kg/hr, P = .80).
Conclusions: The non-invasive stable isotopic method was acceptable and the results provided supporting evidence that Arg/Citr supplementation may increase systemic NO synthesis in children with SCD.

• 出版日期2018-4-1