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

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.

Source: Tosato M, Calvani R, Picca A, Ciciarello F, Galluzzo V, Coelho-Júnior HJ, Di Giorgio A, Di Mario C, Gervasoni J, Gremese E, Leone PM, Nesci A, Paglionico AM, Santoliquido A, Santoro L, Santucci L, Tolusso B, Urbani A, Marini F, Marzetti E, Landi F; Gemelli against COVID-19 Post-Acute Care Team. 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 Nov 23;14(23):4984. doi: 10.3390/nu14234984. PMID: 36501014; PMCID: PMC9738241. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738241/ (Full text)

Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study

Abstract:

PURPOSE: To examine the physiological cost of walking in subjects with chronic fatigue syndrome (CFS) and a matched control group, walking at their preferred and at matched walking speeds.

METHODS: Seventeen people with CFS and 17 matched-controls participated in this observational study of physiological cost during over-ground gait. Each subject walked for 5 min at their preferred walking speed (PWS). Controls then walked for 5 min at the same pace of their matched CFS subject. Gait speed and oxygen uptake, gross and net were measured and oxygen uptake was expressed per unit distance ambulated. CFS subjects completed the CFS-Activities and Participation Questionnaire (CFS-APQ).

RESULTS: At PWS the CFS group walked at a slower velocity of 0.84 +/- 0.21 m s(-1) compared to controls with a velocity of 1.19 +/- 0.13 m s(-1) (p < 0.001). At PWS both gross and net oxygen uptake of CFS subjects was significantly less than controls (p = 0.023 and p = 0.025 respectively). At matched-velocity both gross and net physiological cost of gait was greater for CFS subjects than controls (p = 0.048 and p = 0.001, respectively).

CONCLUSION: The physiological cost of walking was significantly greater for people with CFS compared with healthy subjects. The reasons for these higher energy demands for walking in those with CFS have yet to be fully elucidated.

 

Source: Paul L, Rafferty D, Marshal R. Physiological cost of walking in those with chronic fatigue syndrome (CFS): a case-control study. Disabil Rehabil. 2009;31(19):1598-604. https://www.ncbi.nlm.nih.gov/pubmed/19848558

 

The use of a symptom “self-report” inventory to evaluate the acceptability and efficacy of a walking program for patients suffering with chronic fatigue syndrome

Abstract:

OBJECTIVES: The purpose of this research was to evaluate the effectiveness of the modality of walking as a management strategy for patients suffering with chronic fatigue syndrome (CFS).

METHODS: Six males and fourteen females with medically diagnosed CFS (CDC, 1994), completed a 12-week walking program. Prior to starting the program subjects underwent an incremental walking exercise test to predetermine their walking intensity. The SCL-90-R symptom “self-report” questionnaire was administered prior to, and at the completion of, the walking program.

RESULTS: At the completion of the 12 weeks of walking, changes in four of the nine SCL-90-R dimensions were significant (somatisation, paranoid ideation, phobic anxiety, and psychoticism). Also significant were the changes in the combination indices, the Global Indices of Distress (GID) and the Positive Symptom Total (PST).

CONCLUSION: This group of CFS subjects, by way of “self-report”, indicated the possibility of an exercise-induced decrease in psychological stress. The walking intervention may have evoked positive changes in their well-being and, furthermore, provided no evidence of any exacerbation in their symptoms.

 

Source: Coutts R, Weatherby R, Davie A. The use of a symptom “self-report” inventory to evaluate the acceptability and efficacy of a walking program for patients suffering with chronic fatigue syndrome. J Psychosom Res. 2001 Aug;51(2):425-9. http://www.ncbi.nlm.nih.gov/pubmed/11516764