Oral supplementation with L-homoarginine in young volunteers
Dorothee Atzler, Mirjam Schönhoff, Kathrin Cordts, Imke Ortland, Julia Hoppe, Friedhelm C Hummel, Christian Gerloff, Ulrich Jaehde, Annika Jagodzinski, Rainer H Böger, Chi-Un Choe, Edzard Schwedhelm, Dorothee Atzler, Mirjam Schönhoff, Kathrin Cordts, Imke Ortland, Julia Hoppe, Friedhelm C Hummel, Christian Gerloff, Ulrich Jaehde, Annika Jagodzinski, Rainer H Böger, Chi-Un Choe, Edzard Schwedhelm
Abstract
Aims: 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.
Methods: 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 , Tmax and 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).
Results: 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 AUCs0-24h of 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.
Conclusion: 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.
Keywords: L-arginine; L-homoarginine; asymmetric dimethylarginine; nitric oxide; vascular function.
© 2016 The British Pharmacological Society.
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Source: PubMed