Researchers propose L-arginine blend to restore performance and relieve long Covid

By Nicola Gordon-Seymour

- Last updated on GMT

getty | jongho shin
getty | jongho shin

Related tags COVID-19 Research Vitamin c

L-arginine combined with vitamin C can improve physical performance, muscle strength, endothelial function, and fatigue in adults with long Covid and should be considered a treatment option to relieve persistent symptoms, according to a study published in 'Nutrients'.

Participants taking part in an Italian study administered the supplement blend for between four to eight weeks showed “clinically meaningful improvements” in distance walking, enhanced handgrip strength, as well as reduced fatigue, compared to the placebo.

The “synergistic effects​” of the two compounds enhanced nitric oxide synthesis and bioavailability and ameliorated post-acute Covid-19 symptoms, the study authors write.

Findings align with previous research on the benefits of L-arginine on pulmonary function and aerobic capacity of patients with chronic lung disease, they say.

“A short-term oral administration of L-arginine significantly decreased the mean pulmonary arterial pressure and vascular resistance and improved peak oxygen consumption and dead-space ventilation in patients with precapillary pulmonary hypertension.”

Other tests report oral L-arginine improved outcomes for patients with pulmonary arterial hypertension, congestive heart failure, and after heart transplant surgery.

Study protocol

The single-blind placebo-controlled trial was performed at a post-acute Covid-19 outpatient clinic and included 46 men and women aged 20 and 60 years.

Participants had previously been infected with SARS-CoV-2, had received a negative Covid-19 swab test at least four weeks prior to the trial and a long covid diagnosis, and suffered from persistent fatigue. Serum L-arginine levels were measured prior to the trial and at 28 days.

Eligible participants were randomised to receive twice-daily oral supplementation with either 1.66 g L-arginine and 500 mg liposomal vitamin C, or placebo for 28 days.

The active supplement and placebo were supplied by the Italian pharmaceutical manufacturer, Farmaceutici Damor.

Researchers collected blood samples to assess the difference in physical performance from baseline to 28 days in a six-minute walk test. A hydraulic dynamometer was used to analyse changes in handgrip strength and Doppler ultrasonography to monitor flow-mediated dilation. Finally, fatigue persistence was determined with responses to one item on the Centre for Epidemiological Studies Depression Scale (CES-D).


L-arginine supplementation with 1.5 to 2 g daily from four to seven weeks and 10 to 12 g daily for eight weeks improved both aerobic and anaerobic performance, and participants characterised as ‘untrained’ or ‘moderately trained’ demonstrated the highest gains in exercise performance.

Treatment induced greater improvements in handgrip strength, compared to the placebo. At baseline, approximately 60% of participants had handgrip strength below the 25th​ percentile of age and sex-specific reference values, but the intervention group was more likely to display improved capacity and feature in the first quartile at 28 weeks.

Flow-mediated dilation was also greater after supplementation, with 80% of participants reporting reduced fatigue - the most prevalent symptom in long Covid.

The authors note: “Treatment effects were more evident in women than men. This may be due to the low number of male participants, most of whom were, however, correctly classified in the full model.”


The sample size was small and as such results should be “considered preliminary​”, nevertheless, based on findings, the authors conclude that either acute or chronic L-arginine supplementation could be recommended to enhance aerobic and anaerobic performance.

They add: “While no conclusive evidence exists on the beneficial effects of L-arginine supplementation on human performance, our findings indicate that a short course of L-arginine plus vitamin C supplementation may positively impact the exercise capacity of adults with long COVID​.”

Source: Nutrients

Published online, November 23, 2022:

‘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’

Authors: Matteo Tosato, Riccardo Calvani, Anna Picca, Francesca Ciciarello, Vincenzo Galluzzo, Hélio José Coelho-Júnior, Angela Di Giorgio, Clara Di Mario, Jacopo Gervasoni, Elisa Gremese, Paolo Maria Leone, Antonio Nesci, Anna Maria Paglionico, Angelo Santoliquido, Luca Santoro, Lavinia Santucci, Barbara Tolusso 4, Andrea Urbani, Federico Marini, Emanuele Marzetti and Francesco Landi on behalf of the Gemelli against COVID-19 Post-Acute Care Team

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