L-Citrulline supplementation reduced ICAM-1 and improved 6-minute walk test in post-COVID-19 patients
Background
Post-COVID-19 syndrome is frequently characterized by persistent endothelial dysfunction (ED) and various sequelae, particularly in individuals who experienced critical illness during the acute phase. These long-term effects often impact lung function and the musculoskeletal system, leading to reduced physical capacity. L-citrulline, a nonessential amino acid, has demonstrated potential in improving endothelial function, mitigating systemic inflammation, and enhancing physical performance. This study investigated L-citrulline's effects on ED and body composition in patients grappling with post-COVID-19 syndrome.
Study Design
This open-label randomized controlled clinical trial enrolled 43 adults (≥18 years) who had recovered from COVID-19 and required hospitalization during their acute illness. Participants were randomized 1:1 into two groups: an L-Citrulline 4 g/day intervention group and a control group. The intervention was administered for a duration of three months. Researchers assessed endothelial-related biomarkers including endothelin-1, sE-selectin, ICAM-1, and VCAM-1. Body composition was measured using electrical bioimpedance, and aerobic capacity was quantified via the 6 min walk test (6MWT). Treatment effects were analyzed using two-way repeated-measures ANOVA (group × time).
Results
After three months of follow-up, the L-Citrulline intervention group demonstrated significant improvements compared to the control group. Specifically, ICAM-1 levels decreased substantially in the intervention arm by -32.59 ng/mg of protein (95% CI -52.85 to -12.33), whereas the control group showed a minimal change of -2.31 ng/mg of protein (95% CI -21.59 to 16.95), with a statistically significant difference of p = 0.034. This indicates a marked reduction in an important marker of endothelial activation and inflammation. Furthermore, aerobic capacity, as measured by the 6MWT, saw a notable increase:
The L-Citrulline group improved their walk distance by 141.2 m (95% CI: 98.40 to 184), significantly more than the control group's increase of 67.70 m (95% CI: 30.62 to 104.78), achieving a p = 0.011. This suggests enhanced physical performance. However, no significant differences in body composition were observed between the groups at the end of the follow-up period.
Key Findings
- L-Citrulline supplementation for 3 months significantly decreased
ICAM-1levels by -32.59 ng/mg (p = 0.034) compared to controls. - The L-Citrulline group showed a greater increase in
6MWTdistance by 141.2 m (p = 0.011) compared to controls (67.70 m). - No significant differences in body composition were observed between the L-Citrulline and control groups.
- The intervention targeted adults who required hospitalization during acute COVID-19.
Why It Matters
L-Citrulline supplementation offers a promising, non-pharmacological strategy to address key persistent issues in post-COVID-19 syndrome, specifically endothelial dysfunction and reduced exercise capacity. The observed reduction in ICAM-1 suggests a direct positive impact on vascular health, while the significant improvement in the 6MWT indicates a tangible benefit for patients' physical function and quality of life. The 4 g/day dose and 3-month duration are practical and easily implementable, making this a highly relevant finding for individuals seeking to mitigate long-term COVID-19 sequelae. This could inform future protocols for managing chronic symptoms, potentially improving patient outcomes and reducing the burden of post-viral fatigue and vascular complications.
l-citrulline
post-covid-syndrome
endothelial-dysfunction
exercise-capacity
inflammation
clinical-trial