Effects of Oral L-Citrulline Supplementation on Lipoprotein Oxidation and Endothelial Dysfunction in Humans with Vasospastic Angina
Masahiko Morita, Masami Sakurada, Fumiko Watanabe, Tetsuo Yamasaki, Hiroshi Doi, Hirotaka Ezaki, Koji Morishita and Takayuki Miyake
Affiliation: Tokorozawa Heart Center, 2- 61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
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.
Keywords: Asymmetric dimethylarginine, endothelial dysfunction, flow-mediated dilation, L-Citrulline, nitric oxide, oxidized
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