Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and Persistent Fatigue in Adults with Long COVID: A Single-Blind Randomized Controlled Trial
Tosato et al.,
Effects of l-Arginine Plus Vitamin C Supplementation on Physical Performance, Endothelial Function, and..,
Nutrients, doi:10.3390/nu14234984, NCT04947488
46 patient RCT in Italy showing improved recovery from long COVID symptoms using combined treatment with L-arginine and vitamin C.
Tosato et al., 23 Nov 2022, Single Blind Randomized Controlled Trial, placebo-controlled, Italy, peer-reviewed, 21 authors, trial
NCT04947488 (history).
Contact:
riccardo.calvani@policlinicogemelli.it (corresponding author).
Abstract: nutrients
Article
Effects of L -Arginine Plus Vitamin C Supplementation on
Physical Performance, Endothelial Function, and Persistent
Fatigue in Adults with Long COVID: A Single-Blind
Randomized Controlled Trial
Matteo Tosato 1 , Riccardo Calvani 1, * , Anna Picca 1,2 , Francesca Ciciarello 1 , Vincenzo Galluzzo 1 ,
Hélio José Coelho-Júnior 1,3 , Angela Di Giorgio 1 , Clara Di Mario 4 , Jacopo Gervasoni 1 , Elisa Gremese 1,3,4 ,
Paolo Maria Leone 1 , Antonio Nesci 1 , Anna Maria Paglionico 1 , Angelo Santoliquido 1,5 , Luca Santoro 1 ,
Lavinia Santucci 6 , Barbara Tolusso 4 , Andrea Urbani 1,7 , Federico Marini 8 , Emanuele Marzetti 1,3
and Francesco Landi 1,3 on behalf of the Gemelli against COVID-19 Post-Acute Care Team
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Citation: Tosato, M.; Calvani, R.;
Picca, A.; Ciciarello, F.; Galluzzo, V.;
Coelho-Júnior, H.J.; Di Giorgio, A.; Di
Mario, C.; Gervasoni, J.; Gremese, E.;
et al. Effects of L -Arginine Plus
Vitamin C Supplementation on
Physical Performance, Endothelial
Function, and Persistent Fatigue in
Adults with Long COVID: A
Single-Blind Randomized Controlled
Trial. Nutrients 2022, 14, 4984.
https://doi.org/10.3390/nu14234984
Academic Editors: Bruno Trimarco
and Gaetano Santulli
Received: 13 September 2022
Accepted: 20 November 2022
Published: 23 November 2022
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Copyright: © 2022 by the authors.
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Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy
Department of Geriatrics and Orthopedics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Immunology Core Facility, Gemelli Science Technological Park (GSTeP), Fondazione Policlinico Universitario
A. Gemelli IRCCS, 00168 Rome, Italy
Department of Cardiovascular Sciences, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Metabolomics Research Core Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico
Universitario A. Gemelli IRCCS, 00168 Rome, Italy
Department of Biochemistry and Clinical Biochemistry, Università Cattolica del Sacro Cuore,
00168 Rome, Italy
Department of Chemistry, Sapienza University of Rome, 00185 Rome, Italy
Correspondence: riccardo.calvani@policlinicogemelli.it; Tel.: +39-(06)-3015-5559
Abstract: Long COVID, a condition characterized by symptom and/or sign persistence following
an acute COVID-19 episode, is associated with reduced physical performance and endothelial
dysfunction. Supplementation of L -arginine may improve endothelial and muscle function by
stimulating nitric oxide synthesis. A single-blind randomized, placebo-controlled trial was conducted
in adults aged between 20 and 60 years with persistent fatigue attending a post-acute COVID-19
outpatient clinic. Participants were randomized 1:1 to receive twice-daily orally either a combination
of 1.66 g L-arginine plus 500 mg liposomal vitamin C or a placebo for 28 days. The primary outcome
was the distance walked on the 6 min walk test. Secondary outcomes were handgrip strength,
flow-mediated dilation, and fatigue persistence. Fifty participants were randomized to receive either
L -arginine plus vitamin C or a placebo. Forty-six participants (median (interquartile range) age 51
(14), 30 [65%] women), 23 per group, received the intervention to which they were allocated and
completed the study. At 28 days, L-arginine plus vitamin C..
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