Impact of L-Citrulline Supplementation and HIIT on Lipid Profile, Arterial Stiffness, and Fat Mass in Obese Adolescents with Metabolic-Dysfunction-Associated Fatty Liver Disease: A Randomized Clinical Trial

Overview

Journal Nutrients

Date 2025 Feb 13

PMID 39940261

Authors

Alan Arturo Rodriguez-Carrillo

Mario Ramon Espinoza-Vargas

Katya Vargas-Ortiz

Lorena Del Rocio Ibarra-Reynoso

Monserrat Olvera-Juarez

Armando Gomez-Ojeda

Ma Eugenia Garay-Sevilla

Arturo Figueroa

Affiliations

Soon will be listed here.

Abstract

Background: Metabolic-dysfunction-associated steatotic liver disease (MASLD) and obesity contribute to vascular dysfunction through oxidative stress, heightening cardiovascular risk. Oral supplementation with L-citrulline (L-cit), a precursor of L-arginine (L-arg) and nitric oxide, and high-intensity interval training (HIIT) may improve vascular function and cardiometabolic health.

Objectives: This study aimed to evaluate the combined effects of L-cit supplementation and HIIT on arterial stiffness, body composition, glucose metabolism, lipid profile, and blood pressure (BP) in adolescents with MASLD and obesity.

Methods: In this double-blind, placebo-controlled, randomized clinical trial (ClinicalTrials.gov (NCT05778266), 44 adolescents (15-19 years) with MASLD and obesity were assigned to HIIT + L-cit (n = 14), HIIT + placebo (n = 14), or L-cit (n = 15) for 12 weeks. HIIT sessions (85% and 60% peak heart rate during intense and recovery periods) occurred thrice weekly. Training volume progressively increased, and participants performed 20 min of HITT per session in the last 8 weeks.

Results: Outcomes included pulse wave velocity (PWV), augmentation index (Aix75), VO2peak, body composition, BP, glucose and lipid profiles, and hepatic steatosis. Compared to L-cit, HIIT + L-cit improved non-high-density lipoprotein cholesterol ( = 0.04), very-low-density lipoprotein cholesterol ( = 0.01), triglycerides ( = 0.02), and VO2peak ( = 0.001). No significant between-group changes were found in PWV, AIx75, hepatic steatosis, and body composition. HIIT + placebo improved VO2peak ( = 0.002), and L-cit decreased the degree of steatosis ( = 0.038).

Conclusions: HIIT + L-cit supplementation enhanced lipid profile and cardiorespiratory fitness, while HIIT + placebo improved cardiorespiratory capacity, and L-cit alone decreased hepatic steatosis. Thus, L-cit could be an adjuvant strategy to manage obesity-related MASLD in adolescents.

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