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.


Marealle, AI; Siervo, M; Wassel, S; Bluck, L; Prentice, AM; Minzi, O; Sasi, P; Kamuhabwa, A; Soka, D; Makani, J; Cox, SE; (2018) 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. Nitric oxide. ISSN 1089-8603 DOI: https://doi.org/10.1016/j.niox.2017.12.009

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Abstract

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. Twenty-nine children (70% male, 9-11years, weight 16.3-31.3 kg) with SCD. 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. 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 μmol/kg/hr vs 2.35 ± 1.13 μmol/kg/hr, P = .04). No significant changes were detected in the base RUSF group (weight-adjusted systemic NO synthesis 2.64 ± 1.14 μmol/kg/hr vs 2.53 ± 1.12 μmol/kg/hr, P = .80). 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.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
PubMed ID: 29305240
URI: http://researchonline.lshtm.ac.uk/id/eprint/4646017

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