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
Q1
Nov 2022
Citations:69
Influential Citations:4
Interventional (Human) Studies
93
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Enhanced Details

Methods
Single-center, single-blind, placebo-controlled randomized clinical trial at Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy (1 July 2021–30 April 2022). Participants: adults aged 20–60 years with prior confirmed SARS-CoV-2 infection, negative test within four weeks, long COVID per WHO criteria, and persistent fatigue (CES-D item seven). 50 randomized (25 per group); two withdrew before receiving the allocated intervention and were excluded from analysis. Baseline characteristics were comparable; outcome assessors were blinded; intention-to-treat analyses performed.
Intervention
1.66 g L-arginine plus 500 mg liposomal vitamin C, taken orally twice daily, for 28 days.
Results
Compared with placebo after 28 days, L-arginine plus vitamin C significantly improved several outcomes: serum L-arginine increased by +60.2 µM vs +11.0 µM (p=0.02; mean difference 62.4 µM; 95% CI 11.1–113.7; effect size 0.72); handgrip strength increased by +3.4 kg vs +1.0 kg (p=0.03; 95% CI 0.5–9.4; effect size 0.37); flow-mediated dilation rose to 14.3% vs 9.4% (p=0.03; mean difference 3.4%; 95% CI 0.4–6.5; effect size 0.66); fatigue at day 28: 2/23 active vs 21/23 placebo (p<0.0001). 6-minute walk distance improved more in the active group (clinically meaningful). Active group levels of L-arginine reached those of healthy controls (p=0.8); no adverse events reported. Authors conclude that the combination may restore NO bioavailability and improve exercise capacity, muscle strength, endothelial function, and fatigue in adults with long COVID; may be proposed to relieve persistent symptoms.
Limitations
Small, single-center trial with a modest sample size; short duration (28 days); not powered for sex-specific effects; results may not generalize to broader populations; potential confounders (physical activity, diet) not fully controlled; two withdrawals prior to treatment.

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 muscl...