L-Arginine and Vitamin C Supplementation Improves Physical Performance, Endothelial Function and Fatigue in Adults with Long COVID

by | Jan 11, 2023 | 2022, Amino Acids, Arginine, COVID-19, Vitamin C

Written by Taylor Woosley, Staff Writer. 28-day supplementation of a combination of 1.66 g L-arginine plus 500 mg liposomal vitamin C significantly increased the distance walked on the 6 min walk test (p=0.001), improved handgrip strength (p=0.03) and flow-mediated dilation (p=0.03) compared to placebo. 

feeling illCOVID-19 is a global pandemic that has had a devastating effect on the health and economy of much of human civilization1. While most patients have mild symptoms and recover within several weeks, more than 50% are left with ongoing symptoms several months later2. While the precise definition of long COVID might be lacking, the most common symptoms reported are fatigue and dyspnea that last for months after acute COVID-193. Additional symptoms include breathlessness, palpitation, chest discomfort, peripheral neuropathy, joint pain, abdominal discomfort, and headache4.

There has been numerous research surrounding potential treatments for long COVID, particularly using supplements to reduce symptom severity. One such example is vitamin C, which has been shown to improve symptoms of fatigue and oxidative balance5. Another area of research has focused on L-arginine, a semi-essential amino acid involved in numerous biological processes6. It acts as a substrate for endothelial nitric oxide, while also aiding in regulation of immune responses7.

Tosato et al. conducted a single-blind, randomized controlled trial to analyze the effects of a 28-day oral supplementation with L-arginine plus vitamin C on physical performance, endothelial function, and persistent fatigue in adults with long COVID. Study inclusion consisted of being between 20 and 60 years, with a previous confirmed SARS-CoV-2 infection, experiencing persistent fatigue. Subjects (n=50) were randomized to receive a twice-daily oral supplementation of either a combination of 1.66 g L-arginine plus 500 mg liposomal vitamin C (n=25) or placebo (n=25). The primary endpoint of the study was the change in the distance walked on the 6 min walk test from baseline to day 28. Secondary endpoints included changes in handgrip strength and flow-mediated dilation, and fatigue persistence from baseline to day 28.

Anthropometric measures including body height, weight, and BMI were collected. Blood samples including serum L-arginine were obtained at baseline and after 28 days. Endothelial function was analyzed by measuring the brachial artery dilation following a transient period of forearm ischemia. A Doppler ultrasonography was utilized to measure flow-mediated dilation. Persistence of fatigue was measured based on responses to the Center for Epidemiological Studies Depression Scale (CES-D). Changes from baseline for continuous variables were expressed as deltas and the Student’s t-test was used to evaluate differences between the intervention groups for normally distributed variables or the Mann-Whitney U test for skewed variables. Chi-squared or Fisher tests were used to evaluate differences between groups in categorical variables.

Subjects had a median (IQR) age of 50.5 years and 65.2% were females. Median (IQR) distance walked on the 6 min walk test was 520 m and the handgrip strength was 22.6 kg. Flow-mediated dilation at baseline was 9.8%. The mean (IQR) serum L-arginine concentration was 170.6 µM, with no differences between the two groups. Significant findings of the 28-day study are as follows:

  • At day 28, serum L-arginine concentrations increased more in the L-arginine plus vitamin C group (+60.2 (85.8) µM) than in the placebo group (+11.0 (90.8) µM; p=0.02; mean difference 62.4 µM, 95% CI: 11.1-113.7 µM; effect size=0.72).
  • At day 28, those in the L-arginine plus vitamin C group experienced greater improvements in handgrip strength (+3.4 (7.5) kg) compared with the placebo (+1.0 (6.6) kg, p=0.03; mean difference = 3.4 kg, 95% CI: 0.5−9.4 kg; effect size=0.37).
  • Furthermore, flow-mediated dilation was greater in subjects in the L-arginine plus vitamin C group compared with placebo (14.3% (7.3) vs. 9.4% (5.8), p=0.03; mean difference=3.4%; 95% CI: 0.4–6.5; effect size = 0.66).
  • On day 28, two participants (8.7%) in the L-arginine plus vitamin C group reported fatigue, while 21 participants (80.1%) reported fatigue in the placebo group (p<0.0001).

Results of the study show the efficacy of a combination of L-arginine and liposomal vitamin C on effectively reducing fatigue, while improving physical performance and endothelial function in adults with long COVID. Further research should continue to explore the use of these supplements to better understand how to reduce symptom severity. Study limitations include the small number of participants and the single-center nature of the study, the lack of analyzing sex-specific differences in response to the treatments, and the inability to evaluate L-arginine metabolism more comprehensively in subjects.

Source: Tosato, Matteo, Riccardo Calvani, Anna Picca, Francesca Ciciarello, Vincenzo Galluzzo, Hélio José Coelho-Júnior, Angela Di Giorgio 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 14, no. 23 (2022): 4984.

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

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Posted January 10, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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