PROTEIN, AMINO ACID METABOLISM AND THERAPY: Edited by Rajavel Elango and François MariottiHomoarginine in health and diseaseTsikas, Dimitrios Author Information Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Hannover, Germany Correspondence to Dimitrios Tsikas, Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover 30625, Germany. Tel: +49 511 532 3984; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care 26(1):p 42-49, January 2023. | DOI: 10.1097/MCO.0000000000000889 Buy Metrics Abstract Purpose of review Homoarginine (hArg) is an endogenous, nonproteinogenic amino acid. It is enzymatically synthesized from L-arginine and L-lysine. Low hArg concentrations appear to be a risk factor in the renal and cardiovascular systems. This review discusses advances in-vitro and in-vivo experimental and clinical research on hArg in health and disease. Recent findings Recent studies indicate that low circulating and low urinary concentrations of hArg are associated with morbidity and worse outcome. Although the biological activities of hArg remain still unexplored, hArg supplementation is intensely investigated as a strategy to increase hArg concentration to reach normal levels in cases of low hArg concentrations. The greatest changes in circulating hArg concentrations are observed during pregnancy and after delivery. In healthy adults, a daily dose of 125 mg hArg seems to be optimum to normalize circulating levels. Short-term supplementation of inorganic nitrate enhances hArg biosynthesis in healthy young men. Apart from hArg supplementation, dietary L-arginine and L-citrulline appear to be a promising alternative. Summary Considerable progress has been made in recent years, but hArg remains still enigmatic. Further research is required to explore the biological activities of hArg. Supplementation of hArg or its precursors L-citrulline/L-arginine seem to be promising strategies to prevent and overcome altered hArg synthesis. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.