# 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 PMID: 39940261 Journal: Nutrients Published: 2025 Jan 23 Authors: Rodríguez-Carrillo AA, Espinoza-Vargas MR, Vargas-Ortiz K, Ibarra-Reynoso LDR, Olvera-Juárez M, Gómez-Ojeda A, Garay-Sevilla ME, Figueroa A ## Question Does combining L-citrulline supplementation with HIIT improve arterial stiffness, body composition, glucose metabolism, lipid profile, blood pressure, VO2peak, and hepatic steatosis in adolescents with MASLD and obesity? ## Summary This double-blind randomized clinical trial tested HIIT plus L-citrulline, HIIT plus placebo, and L-citrulline alone in adolescents with obesity and metabolic-dysfunction-associated steatotic liver disease. HIIT plus L-citrulline improved VO2peak and several lipid measures compared with L-citrulline alone, while HIIT plus placebo improved VO2peak. No significant between-group changes were found for arterial stiffness, body composition, or hepatic steatosis, although the HIIT plus L-citrulline group improved some of those measures within group. ## Population - Adolescents with obesity and metabolic-dysfunction-associated steatotic liver disease. - Sample size: 43 - Age: 15-19 years. - Sex: 33 female and 9 male reported in randomized allocation text, with one apparent sex-count inconsistency in the article. - Fitness level: Sedentary; no structured exercise for at least 6 months. - Health status: MASLD and obesity; Tanner stage IV or V; non-smokers; no chronic diseases; some had normal, elevated, or hypertensive blood pressure. ## Methodology - Randomized double-blind placebo-controlled parallel-group clinical trial with HIIT + L-citrulline, HIIT + placebo, and L-citrulline-only groups. - 12 weeks. - High-school recruitment in Leon, Guanajuato, Mexico; supervised stationary-bike training and clinical/laboratory assessments. - Randomized and controlled study design. ## Protocol - Supervised cycling HIIT plus L-citrulline or placebo. - Modality: Stationary cycling. - Work intervals: Total intense-period volume progressed from 6 minutes/session to 8 minutes/session to 10 minutes/session. - Recovery: Equal recovery volume at 60% HRpeak. - Sets or repetitions: 6, 8, then 10 intense/recovery units as volume progressed. - Intensity: 85% HRpeak during intense periods; 60% HRpeak during recovery. - Session duration: 5-minute warm-up, interval block, 5-minute cooldown; 20-minute HIIT block in final 8 weeks. - Frequency: 3 sessions/week. - Program length: 12 weeks. - Progression: Weeks 1-2: 6 minutes intense plus 6 minutes recovery; weeks 3-4: 8 plus 8; weeks 5-12: 10 plus 10. - L-citrulline alone and HIIT + placebo. - Modality: Capsules alone for L-citrulline group; same cycling HIIT plus placebo capsules for placebo group. - Work intervals: Same HIIT protocol for HIIT + placebo; none for L-citrulline-only group. - Recovery: Same HIIT protocol for HIIT + placebo; none for L-citrulline-only group. - Sets or repetitions: Same HIIT protocol for HIIT + placebo; none for L-citrulline-only group. - Intensity: Same 85%/60% HRpeak HIIT for HIIT + placebo. - Session duration: Same HIIT duration for HIIT + placebo. - Frequency: 3 HIIT sessions/week for HIIT + placebo. - Program length: 12 weeks. - Progression: Same HIIT progression for HIIT + placebo; L-citrulline-only took 6.6 g/day capsules. ## Outcomes ### VO2peak Status: improved HIIT + L-citrulline and HIIT + placebo improved VO2peak, with HIIT + L-citrulline superior to L-citrulline alone. HIIT + L-cit vs L-cit p=0.001; HIIT + placebo improved VO2peak p=0.002. ### Lipids Status: improved HIIT + L-citrulline improved non-HDL-C, VLDL-C, and triglycerides compared with L-citrulline alone. Non-HDL-C p=0.04; VLDL-C p=0.01; triglycerides p=0.02. ### Arterial stiffness, steatosis, and body composition Status: no clear change No significant between-group changes were found for PWV, AIx75, hepatic steatosis, or body composition. Reported as no significant between-group changes. ### Within-group HIIT + L-citrulline changes Status: mixed Within the HIIT + L-citrulline group, BMI, fat mass, body fat percentage, visceral fat area, VLDL-C, triglycerides, SBP, and PWV improved. BMI p=0.03; fat mass/body fat p=0.02; visceral fat area p=0.02; VLDL-C p=0.007; TG p=0.01; SBP p=0.01; PWV p<0.001. ### Hepatic steatosis Status: mixed L-citrulline alone decreased steatosis grade, whereas the HIIT groups did not significantly change steatosis grade. L-citrulline p=0.038. ## Practical Insights - For clinical adolescents with MASLD and obesity, supervised cycling HIIT improved fitness but did not by itself improve liver steatosis in this trial. - Supplement co-interventions should be separated from exercise-only claims. - Progressive cycling volume and HR monitoring supported high adherence. ## Limitations - Small sample size powered for PWV rather than all outcomes. - No placebo/no-HIIT inactive control group. - Mostly female sample and clinical MASLD/obesity population limit generalizability. - Liver fat was assessed by ultrasonography, which may miss subtle changes. - No dietary regimen was included. ## Safety And Adherence - No adverse effects to supplements were reported. - No injuries related to exercise training were reported. - Participants were clinically screened, including ECG before exercise stress testing. ## Original Sources - [PubMed](https://pubmed.ncbi.nlm.nih.gov/39940261/) (pubmed) - [DOI](https://doi.org/10.3390/nu17030402) (doi) - [PMC full text](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11820369/) (full text) ## Agent Guidance Preserve the paper-level scope of this note. Do not generalize beyond the population, protocol, measured outcomes, and limitations above.