Effects of l-Arginine Plus Vitamin C Supplementation on l-Arginine Metabolism in Adults with Long COVID: Secondary Analysis of a Randomized Clinical Trial
Riccardo Calvani, Jacopo Gervasoni, Anna Picca, Francesca Ciciarello, Vincenzo Galluzzo, Hélio José Coelho-Júnior, Clara Di Mario, Elisa Gremese, Sara Lomuscio, Anna Maria Paglionico, Lavinia Santucci, Barbara Tolusso, Andrea Urbani, Federico Marini, Emanuele Marzetti, Francesco Landi, Matteo Tosato
International Journal of Molecular Sciences, 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.
Author Contributions: Conceptualization, R.C., J.G., M.T. and F.L.; methodology, A.P., H.J.C.-J., C.D.M., J.G., E.G., S.L., L.S. and B.T.; validation, A.U. and E.M.; formal analysis, M.T., R.C., H.J.C.-J. and F.M.; investigation, F.C., V.G. and A.M.P.; resources, E.G., A.U. and F.L.; writing-original draft preparation, R.C.; writing-review and editing, J.G., M.T. and E.M.; supervision, A.U. and F.L. All authors have read and agreed to the published version of the manuscript.
Conflicts of Interest: The authors declare no conflict of interest. L-arginine plus vitamin C supplement and placebo were donated by Farmaceutici Damor, Naples, Italy. The supplier had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.
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'abstract': '<jats:p>Altered l-arginine metabolism has been described in patients with COVID-19 and has '
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'determined the serum concentrations of l-arginine, citrulline, ornithine, '
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'URL': 'http://dx.doi.org/10.3390/ijms24065078',
'relation': {},
'ISSN': ['1422-0067'],
'subject': [],
'container-title-short': 'IJMS',
'published': {'date-parts': [[2023, 3, 7]]}}
