Evidence mapPaperPMID 36501014Full record

Trial reportNutrients2022

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, Riccardo Calvani, Anna Picca, Francesca Ciciarello, Vincenzo Galluzzo, Hélio José Coelho-Júnior, Angela Di Giorgio, Clara Di Mario, Jacopo Gervasoni, Elisa Gremese and 12 more

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Nutrients, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
10.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Pooled it
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  17. Review
  18. Interventions for Long COVID: A Narrative Review.Journal of general internal medicine · 2025
    Review
  19. Article
  20. Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 1 country.

Matteo TosatoFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0001-5750-9746
Riccardo CalvaniFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0001-5472-2365
Anna PiccaFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0001-7032-3487
Francesca CiciarelloFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Vincenzo GalluzzoFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0003-4620-5979
Hélio José Coelho-JúniorFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0001-7482-9514
Angela Di GiorgioFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Clara Di MarioImmunology Core Facility, Gemelli Science Technological Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Jacopo GervasoniFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0002-3600-392X
Elisa GremeseFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Paolo Maria LeoneFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0002-7868-8410
Antonio NesciFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Anna Maria PaglionicoFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Angelo SantoliquidoFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Luca SantoroFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0003-3614-7314
Lavinia SantucciMetabolomics Research Core Facility, Gemelli Science and Technology Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0002-7448-0604
Barbara TolussoImmunology Core Facility, Gemelli Science Technological Park (GSTeP), Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Andrea UrbaniFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Federico MariniDepartment of Chemistry, Sapienza University of Rome, 00185 Rome, Italy.ORCID 0000-0001-8266-1117
Emanuele MarzettiFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.ORCID 0000-0001-9567-6983
Francesco LandiFondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy.
Gemelli against COVID-19 Post-Acute Care Team
Agostino Gemelli University Polyclinic · ITUniversità Cattolica del Sacro Cuore · ITLibera Università Maria SS. Assunta · ITSapienza University of Rome · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 increased the 6 min walk distance (+30 (40.5) m; placebo: +0 (75) m, p = 0.001) and induced a greater improvement in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1 (6.6) kg, p = 0.03). The flow-mediated dilation was greater in the active group than in the placebo (14.3% (7.3) vs. 9.4% (5.8), p = 0.03). At 28 days, fatigue was reported by two participants in the active group (8.7%) and 21 in the placebo group (80.1%; p < 0.0001). l-arginine plus vitamin C supplementation improved walking performance, muscle strength, endothelial function, and fatigue in adults with long COVID. This supplement may, therefore, be considered to restore physical performance and relieve persistent symptoms in this patient population.

Indexed as

COVID-19Post-Acute COVID-19 SyndromeAdultArginineAscorbic AcidDouble-Blind MethodFatigueFemaleHand StrengthHumansMaleMiddle AgedPhysical Functional PerformanceSingle-Blind MethodVitaminsYoung AdultArginineAscorbic AcidVitamins6 min walk testflow-mediated dilationhandgrip strengthnitric oxidenutraceuticalsoral supplementpersistent symptomspost-acute COVID-19 syndromeSARS-CoV-2

Identifiers

PMID36501014
PMCPMC9738241
OpenAlexW4310036639

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.