Effect of L-citrulline and HIIT on Arterial Stiffness, Body Composition, and Lipid Profile in Adolescents with Steatosis Associated with Metabolic Dysfunction (MASLD)

Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) accelerate the appearance of arterial stiffness due to inflammatory and oxidative stress mechanisms producing increased vascular tone and increasing the risk of cardiovascular disease. This arterial stiffness can be measured through pulse wave velocity (PWV). Obesity and MAFLD have multifactorial components, high fructose diet and sedentary lifestyle are causing the onset of these diseases earlier in life such as in adolescence. L-citrulline, a non-protein amino acid, has shown positive effects on improving nitric oxide synthesis which improves endothelial function, as well as results on the metabolic profile in MASLD. High intensity interval training (HIIT) has also shown benefits on endothelial function improving the metabolic profile of people with obesity and MASLD with the advantage of decreasing the time required to perform the physical activity. A clinical study will be conducted with 45 adolescents (15-19 years old) with MASLD and the participants will be divided into 3 groups to perform HIIT and supplement with citrulline or placebo for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Obesity, Adolescent; Arterial Stiffness; Metabolic Dysfunction-Associated Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: L-citrulline; Other: High Intensity Intervals Training; Dietary supplement: Carboxymethyl cellulose

Detailed Description

The investigators hypothesize that citrulline and HIIT have additive effects on endothelial function in people with obesity and MASLD, in addition to improving metabolic, lipid and hepatic steatosis profile. the researcher´s aim is to evaluate the effect of citrulline and HIIT on arterial stiffness assessed by PWV in adolescents with MASLD. For this the investigators will perform a randomized, double-blind clinical study in 45 adolescents with MASLD and obesity, who will be supplemented with 6 g per day with L-citrulline or placebo (Carboxymethylcellulose) and will perform HIIT sessions for 12 weeks. At the beginning and at the end of the intervention, the level of arterial stiffness by means of PWV, body composition, biochemical and metabolic data, as well as the degree of hepatic steatosis will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Guanajuato
    • León, Guanajuato, Mexico, 37000
      • Universidad de Guanajuato

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of obesity and metabolic associated-dysfunction steatotic liver disease associated with (MASLD) and with moderate or severe steatosis
• History of physical inactivity
• They should not be under treatment with any dietary supplement or polyvitamins for weight loss at least 6 months before the study.
• They should not be smokers.
• Not have a diagnosis of any chronic degenerative disease
• Adolescents without fracture or musculoskeletal injury
• Patients without surgical procedures at least 1 month prior to the protocol.
• Women who are not pregnant or use oral contraceptives

Exclusion Criteria:

• Participants who do not complete at least 80% of the training sessions.
• Participants who miss 2 consecutive weeks of training.
• Who do not ingest the L-citrulline supplement or placebo.
• Participants who present allergy or intolerance to L-citrulline.
• Participants who present any injury during the intervention period that prevents them from performing the training.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: L-Cit + HIIT; adolescents will be supplemented with 6 g/day of L-citrulline and 3 sessions per week of HIIT for 12 weeks	Dietary supplement: L-citrulline; oral supplementation of pure L-citrulline (6 g) for twelve weeks; Other: High Intensity Intervals Training; participants will have sessions 3 days a week for twelve weeks; Other Names: HIIT
Active Comparator: L-Cit; adolescents will be supplemented with 6 g/day of L-citrulline but without do exercise for 12 weeks	Dietary supplement: L-citrulline; oral supplementation of pure L-citrulline (6 g) for twelve weeks
Placebo Comparator: Placebo + HIIT; adolescents will be supplemented with 6 g/day of Carboxymethyl cellulose and 3 sessions per week of HIIT for 12 weeks	Other: High Intensity Intervals Training; participants will have sessions 3 days a week for twelve weeks; Other Names: HIIT; Dietary supplement: Carboxymethyl cellulose; oral supplementation of Carboxymethyl cellulose (6 g) as a placebo, for twelve weeks; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arterial Stiffness	The degree of arterial stiffness will be evaluated by oscillometric device (Mobil-O Graph). This device assesses Pulse Wave Velocity	12 weeks
Reflected Wave	The Augmentation Index (AIx) measures the percentage of the pressure increase that is caused by the premature arrival of the reflected wave and is expressed as the ratio of PAo and PP multiplied by 100. AIx@75 is AIx corrected to a heart rate of 75 beats per minute. The Mobil-O Graph device also evaluates AIx@75	12 weeks
Degree of hepatic steatosis	The degree of hepatic steatosis will be evaluated by abdominal ultrasound. It will be diagnosed as: Moderate, when sound attenuation is added.; Severe, when the wall of the portal vessels and the diaphragm are not visible.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose metabolism: glucose	Glucose will be evaluated by the Lakeside glucose oxidase method (GOD-PAPTM).	12 weeks
Glycated hemoglobin (HbA1c)	Glycated hemoglobin (HbA1c) will be measured by reflectance spectrophotometry, by boronic acid affinity.	12 weeks
Insuline Resistance	Insulin level will be measured by ELISA (ALPCO) method. The Homeostatic Model Assessment Index (HOMA-IR) will be calculated to determine insulin resistance.	12 weeks
Lipid profile	The lipid profile will be measured by the modified Huang method.	12 weeks
VO2max	VO2max is a measure of aerobic exercise capacity. It will be performed on a cycloergometer. Every 2 minutes 0.5 kp will be increased and HR will be measured minute by minute with a portable monitor (Polar HO1). When the participant no longer maintains the 60 rpm cadence or reaches the maximum perceived exertion on the modified Borg scale (9 or 10), the test is terminated.	12 weeks
Arterial Pressure	Is pressure exerted by the blood on the artery wall. The mobil-O Graph also evaluates arterial pressure and reports it as Dyastolic Pressure (DAP), Systolic Pressure (SAP) and Mean Arterial Pressure (MAP)	12 weeks
Body composition	Bioelectrical impedance will be used to assess total body composition as fat free mass (FFM), fat mass (FM) and total body water, using the standard configuration. The portable, multi-frequency In body S10 device will be used and it reports body composition in percentage (%)	12 weeks

Collaborators and Investigators

• Sponsor: Universidad de Guanajuato
• Investigators: Principal Investigator: Ma. Eugenia Garay-Sevilla, PhD, Universidad de Guanajuato; Study Chair: Alan Arturo Rodriguez-Carrillo, Bachelor, Universidad de Guanajuato

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2023
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): April 30, 2024

Study Registration Dates

• First Submitted: February 19, 2023
• First Submitted That Met QC Criteria: March 18, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Adolescents; Obesity; HIIT; PWV; MAFLD; L-citrulline supplementation; AIx75
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Digestive System Diseases; Overweight; Obesity; Liver Diseases; Fatty Liver; Pediatric Obesity; Gastrointestinal Agents; Laxatives; Carboxymethylcellulose Sodium
• Other Study ID Numbers: PWV-MAFLD-HIIT-CITRULLINE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: At the request of the researcher

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No