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Atzler, Dorothee; Schönhoff, Mirjam; Cordts, Kathrin; Ortland, Imke; Hoppe, Julia; Hummel, Friedhelm C.; Gerloff, Christian; Jaehde, Ulrich; Jagodzinski, Annika; Böger, Rainer H.; Choe, Chi-un; Schwedhelm, Edzard (2016): Oral supplementation with L-homoarginine in young volunteers. In: British Journal of Clinical Pharmacology, Vol. 82, No. 6: pp. 1477-1485
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Abstract

AimsLow 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. MethodsIn a double-blind, randomized, placebo-controlled crossover study, 20 young volunteers received 125mg L-hArg once daily for 4 weeks. Kinetic parameters (C-max, T-max and AUC(0-24h)) 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). ResultsOne hour after ingestion (T-max), L-hArg increased the baseline L-hArg plasma concentration (2.87 0.91moll(-1), mean +/- SD) by 8.74 +/- 4.46 [95% confidence intervals 6.65;10.9] and 17.3 +/- 4.97 [14.9;19.6] moll(-1) (C-max), after single and multiple doses, respectively. Once-only and 4 weeks of supplementation resulted in AUCs(0-24h) of 63.5 +/- 28.8 [50.0;76.9] and 225 +/- 78.5 [188;2624] moll(-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. ConclusionOnce daily orally applied 125mg 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.