L-Citrulline Improves Liver Steatosis in Adolescents

by | Apr 8, 2025 | 2025, Amino Acids, Citrulline, Infant and Children's Health, Liver Health, Obesity, Recent Articles

Written by Chrystal Moulton, Science Writer. In the L-citrulline only group, researchers observed a significant improvement in liver steatosis level.

liver healthObesity is a chronic condition associated with an increase in cardiovascular disease, diabetes, and liver steatosis1,2. Research demonstrates that excessive intake of fat and carbohydrates increases free fatty acids in the liver, promotes inflammation, and insulin resistance which ultimately leads to the development of liver steatosis3. The chain reaction of events linking obesity to liver steatosis also contributes to endothelial dysfunction by reducing nitric oxide production4. Supplementation with L-citrulline, a precursor to L-arginine, has demonstrated positive effects in improving endothelial function5,6 while lowering liver steatosis7, LDL-C8, and blood pressure9,10 in middle aged adults. In the current trial, researchers investigated the effects of L-citrulline supplementation and high-intensity interval training (HIIT) on children with metabolic-dysfunction-associated steatotic liver disease (MASLD) previously known as non-alcoholic fatty liver disease (NAFLD)11.

This study was designed as a double-blind, randomized, parallel group trial which lasted for 12 weeks. Children between 15-19 years old who were diagnosed with liver steatosis with a BMI >30kg/m2 were included in this trial. These children were non-smokers with no history of using exercise programs, supplements, or medications and lived a sedentary lifestyle. Eligible participants were randomly assigned to 1 of 3 groups:

  • HIIT w/ L-citrulline (n=15)- participants were given 6.6g of citrulline in the form of 737mg capsules [5 capsules in the morning and 4 at night before breakfast and dinner, respectively]. HIIT was done on a stationary bike 3 times a week. The exercise load and sets increased progressively over the duration of the trial. Children were closely monitored and instructed to cycle until exhaustion.
  • HIIT w/ placebo (n=14)– participants took carboxymethylcellulose capsules in the same manner as the HIIT w/ L-citrulline group. Placebo capsules looked like L-citrulline in size and color. HIIT was done on a stationary bike 3 times a week. The sets increased progressively over the duration of the trial. Children were closely monitored and instructed to cycle until exhaustion.
  • L-citrulline (n=14)- participants were given 6.6g of citrulline in the form of 737mg capsules [5 capsules in the morning and 4 at night before breakfast and dinner, respectively]. No exercise routine given. Children maintained their current sedentary lifestyle.

Bioelectric impedance was used to determine fat mass to lean muscle. Ultrasound was used to assess the degree of liver steatosis. Anthropometric measurements and blood samples were also taken to assess lipid profile and insulin resistance (HOMA-IR). Measurements were conducted at baseline and week 12.

Of 43 participants randomly allocated to each group, data from 33 participants were eligible for analysis. Compliance was over 90% in all groups. No significant differences were observed in baseline characteristics between groups. Researchers observed a significant improvement within the HIIT w/ L-citrulline supplementation group in pulse wave velocity [a measure of arterial stiffness] (P<0.001), BMI (P=0.03), body fat mass (P=0.02), visceral fat (P=0.02), VLDL-C (P=0.007), triglycerides (P=0.01), systolic blood pressure (P=0.01) and VO2 peak (P=0.002). The HIIT w/ placebo group had a significant increase in VO2 peak (P<0.0001) and total cholesterol (P=0.008). No changes in liver steatosis were observed in the HIIT w/ citrulline or placebo groups. In the L-citrulline only group, researchers observed a significant improvement in liver steatosis level. Specifically within the L-citrulline, all 3 participants with severe liver steatosis improved to moderate by week 12. Also, 4 out of 6 participants went from moderate to mild steatosis by week 12. No adverse effects of HIIT or supplementation were observed.

Results from the trial suggest L-citrulline supplementation alone improved liver steatosis in adolescents. Furthermore, HIIT training w/ L-citrulline supplementation improved visceral fat, fat mass, systolic blood pressure, VLDL-C, triglycerides, and pulse wave velocity. Additional studies will be needed to verify these findings and elucidate the combination of HIIT and L-citrulline supplementation the improves liver steatosis while reducing fat mass in obese adolescents.

Source: Rodríguez-Carrillo, Alan Arturo, Mario Ramón Espinoza-Vargas, Katya Vargas-Ortiz, Lorena del Rocío Ibarra-Reynoso, Monserrat Olvera-Juárez, Armando Gómez-Ojeda, Ma Eugenia Garay-Sevilla, and Arturo Figueroa. “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.” Nutrients 17, no. 3 (2025): 402.

© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/
licenses/by/4.0/).

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Posted April 8, 2025.

Chrystal Moulton BA, PMP, is a 2008 graduate of the University of Illinois at Chicago. She graduated with a bachelor’s in psychology with a focus on premedical studies and is a licensed project manager. She currently resides in Indianapolis, IN.

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