title: Oral supplementation with L-homoarginine in young volunteers.
abstract: Low blood concentrations of the naturally occurring amino acid L-homoarginine (L-hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L-hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L-hArg supplementation.
  
  
  
  In a double-blind, randomized, placebo-controlled crossover study, 20 young volunteers received 125 mg L-hArg once daily for 4 weeks. Kinetic parameters (Cmax, Tmaxand AUC0-24h) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L-arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow-mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF).
  
  
  
  One hour after ingestion (Tmax), L-hArg increased the baseline L-hArg plasma concentration (2.87 ± 0.91 μmol l-1, mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] μmol l-1(Cmax), after single and multiple doses, respectively. Once-only and 4 weeks of supplementation resulted in AUCs0-24hof 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] μmol l-1*h, for single and multiple doses, respectively. Routine laboratory parameters, L-arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L-hArg supplementation compared to baseline.
  
  
  
  Once daily orally applied 125 mg L-hArg raises plasma L-hArg four- and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.|Vascular Biology, Institute for Stroke and Dementia Research, Klinikum der Universität München Ludwig Maximilians-University of Munich, Munich, Germany.
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Schönhoff
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Cordts
authors.affiliation: Institute of Pharmacy Department of Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Imke
authors.initials: I
authors.lastname: Ortland
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Hoppe
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Friedhelm C
authors.initials: FC
authors.lastname: Hummel
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gerloff
authors.affiliation: Institute of Pharmacy Department of Clinical Pharmacy, University of Bonn, Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Jaehde
authors.affiliation: DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.|Department of General and Interventional Cardiology, University Heart Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Jagodzinski
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.affiliation: Department of Neurology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Choe
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.|DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D002319:Cardiovascular System / Q000187:drug effects*; D018592:Cross-Over Studies; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D064368:Healthy Volunteers; D006709:Homoarginine / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D006709:Homoarginine
keywords: L-arginine; L-homoarginine; asymmetric dimethylarginine; nitric oxide; vascular function