Oral supplementation with L‐homoarginine in young volunteers

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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.

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