Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial

• Published in: International journal of molecular sciences 2023-03, Vol.24 (6), p.5078
• Main Authors: Calvani, Riccardo, Gervasoni, Jacopo, Picca, Anna, Ciciarello, Francesca, Galluzzo, Vincenzo, Coelho-Júnior, Hélio José, Di Mario, Clara, Gremese, Elisa, Lomuscio, Sara, Paglionico, Anna Maria, Santucci, Lavinia, Tolusso, Barbara, Urbani, Andrea, Marini, Federico, Marzetti, Emanuele, Landi, Francesco, Tosato, Matteo
• Format: Article
• Language: English
• Subjects: Accuracy; ADMA; Adult; Adults; Arginine; Arginine - metabolism; Ascorbic acid; Ascorbic Acid - therapeutic use; Bioavailability; Citrulline; Citrulline - metabolism; Classification; Clinical trials; Comparative analysis; Coronaviruses; COVID-19; Dietary Supplements; Discriminant analysis; flow-mediated dilation; Health aspects; Hospitals; Humans; Infection; Infections; Long COVID; Medical laboratories; Metabolism; Metabolites; Monomethyl-L-arginine; Mortality; Nitric oxide; Nitric Oxide - metabolism; nutraceuticals; Ornithine; Physiological aspects; Placebos; Post-Acute COVID-19 Syndrome; Product development; SARS-CoV-2; SARS-CoV-2 - metabolism; Severe acute respiratory syndrome coronavirus 2; Vitamin C
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065078

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS-DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS-DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID.