title: Effects of Oral L-Citrulline Supplementation on Lipoprotein Oxidation and Endothelial Dysfunction in Humans with Vasospastic Angina.
abstract: 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 after supplementation.
  
  
  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 L-arginine/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.
authors.affiliation: Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigao-ka, Tsukuba, Ibaraki 305-0841, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Morita
authors.affiliation: Tokorozawa Heart Center, 2-61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Sakurada
authors.affiliation: Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigao-ka, Tsukuba, Ibaraki 305-0841, Japan.
authors.forename: Fumiko
authors.initials: F
authors.lastname: Watanabe
authors.affiliation: Tokorozawa Heart Center, 2-61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamasaki
authors.affiliation: Tokorozawa Heart Center, 2-61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Doi
authors.affiliation: Tokorozawa Heart Center, 2-61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Ezaki
authors.affiliation: Function Research Group, Healthcare Products Development Center, KYOWA HAKKO BIO CO., LTD., 2, Miyukigao-ka, Tsukuba, Ibaraki 305-0841, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Morishita
authors.affiliation: Tokorozawa Heart Center, 2-61-11, Kamiarai, Tokorozawa, Saitama 359-1142, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyakex
keywords: Asymmetric dimethylarginine; L-Citrulline; endothelial dysfunction; flow-mediated dilation; nitric oxide; oxidized LDL.