Effect of L-Citrulline Supplementation on Endothelial Function and Body Composition in Post-COVID-19 Syndrome: A Randomized Clinical Trial

Background: Post-COVID-19 syndrome is associated with endothelial dysfunction (ED) and various sequelae, particularly in individuals who experienced critical illness during the acute phase, affecting lung function and the musculoskeletal system. L-citrulline, a nonessential amino acid, has been shown to improve endothelial function, systemic inflammation, blood pressure, and physical performance. This study aimed to assess the effects of L-citrulline supplementation on ED and body composition in patients with post-COVID-19 syndrome. Methods: We conducted an open-label randomized controlled clinical trial at the Instituto Nacional de Enfermedades Respiratorias in Mexico City, Mexico, from February 2021 to May 2022. Eligible subjects were adults aged ≥18 years who recovered from COVID-19 and required hospitalization during acute COVID-19. Participants were randomized 1:1 into two groups: (1) the L-citrulline group (4 g/day) and (2) the control group. The intervention lasted three months. Endothelial-related biomarkers, including endothelin-1, sE-selectin, ICAM-1, and VCAM-1, were investigated. Body composition was measured using electrical bioimpedance, and aerobic capacity was assessed with the 6 min walk test (6MWT). Treatment effects were analyzed using two-way repeated-measures ANOVA (group × time). Results: In total, 43 subjects participated in the study. After three months of follow-up, the intervention group showed a decrease in ICAM-1 (−32.59 ng/mg of protein; 95% CI −52.85 to −12.33 vs. −2.31 ng/mg of protein, CI 95%: −21.59 to 16.95, p = 0.034) and an increase in 6MWT (141.2 m; 95% CI: 98.40 to 184 vs. 67.70 m, CI 95%: 30.62 to 104.78, p = 0.011) compared with the control group. No differences in body composition were observed between the groups at follow-up. Conclusions: L-citrulline supplementation for three months decreased ICAM-1 and increased 6MWT.