PMID 39940261

Research
All papers

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

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.

Methodology

  • Adolescents with obesity and metabolic-dysfunction-associated steatotic liver disease.
  • 43 participants.
  • 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.
  • Intensity: 85% HRpeak during intense periods; 60% HRpeak during recovery.
  • 5-minute warm-up, interval block, 5-minute cooldown; 20-minute HIIT block in final 8 weeks.
  • 3 sessions/week.
  • 12 weeks.
  • Randomized double-blind placebo-controlled parallel-group clinical trial with HIIT + L-citrulline, HIIT + placebo, and L-citrulline-only groups.
  • Cardiorespiratory fitness, Lipids and glucose metabolism, Arterial stiffness, and Body composition were tracked.

Outcomes

VO2peak

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.

Improved

Lipids

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.

Improved

Arterial stiffness, steatosis, and body composition

No significant between-group changes were found for PWV, AIx75, hepatic steatosis, or body composition.

Reported as no significant between-group changes.

No clear change

Within-group HIIT + L-citrulline changes

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.

Mixed

Hepatic steatosis

L-citrulline alone decreased steatosis grade, whereas the HIIT groups did not significantly change steatosis grade.

L-citrulline p=0.038.

Mixed

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

  • 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.