Background: Decreased nitric oxide (NO) bioavailability and increased lipid oxidation are associated with progressive
endothelial dysfunction. L-Citrulline, the effective precursor of L-arginine which is essential as a substrate for
endothelial NO synthase (eNOS), is effective in enhancing NO-dependent signaling. However, little is known about the
efficacy of L-citrulline supplementation on lipoprotein oxidation and endothelial dysfunction.
Methods: Twenty-two patients (aged 41 - 64 years old) diagnosed with vasospastic angina with flow-mediated dilation
(FMD) of the brachial artery (< 5.5 %) received 800 mg/day of L-citrulline for 8 weeks. FMD (%), blood NOx, asymmetric
dimethylarginine (ADMA), small dense LDL, oxidized lipids, amino acids concentrations were measured before and
Results: Compared with baseline values, FMD (%) was significantly improved at 4 and 8 weeks as well as at 4 weeks after
the end of intake. L-Citrulline supplementation caused a significant lowering of plasma ADMA levels. Plasma Larginine/
ADMA ratio and NOx levels rose markedly throughout the study period. Moreover, significant reductions of serum
oxidized LDL and lectin-like oxidized LDL receptor 1 (LOX-1) ligand containing ApoB (LAB), an indicator of the
biological activity of oxidized lipoprotein binding to LOX-1, were observed after L-citrulline intake.
Conclusions: L-Citrulline supplementation improves endothelial dysfunction, probably due to potentiating NO-dependent
reactions and decreasing the state of lipoprotein oxidation in humans.