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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

Lookup NU author(s): Dr Mario Siervo



This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).


© 2018 The Authors 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 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). 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.

Publication metadata

Author(s): Marealle AI, Siervo M, Wassel S, Bluck L, Prentice AM, Minzi O, Sasi P, Kamuhabwa A, Soka D, Makani J, Cox SE

Publication type: Article

Publication status: Published

Journal: Nitric Oxide

Year: 2018

Volume: 74

Pages: 19-22

Print publication date: 01/04/2018

Online publication date: 02/01/2018

Acceptance date: 29/12/2017

Date deposited: 22/01/2018

ISSN (print): 1089-8603

ISSN (electronic): 1089-8611

Publisher: Academic Press Inc.


DOI: 10.1016/j.niox.2017.12.009


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