:: Volume 14, Issue 3 (Autumn 2019) ::
2019, 14(3): 1-9 Back to browse issues page
Effects of Citrulline on Non-alcoholic Fatty Liver Disease: A Randomized-controlled Clinical Trial
Z Darabi , M Darand, Z Yari , Sh Agah , A Hrkmat doust Doctor *
Abstract:   (1651 Views)
Background and Objectives: Citrulline (cit.) is a non-essential amino acid derived from watermelon, which affects improving glucose tolerance and lipid and energy metabolisms. The aim of this study was to investigate effects of citrulline supplementation on non-alcoholic fatty liver.
 Materials & Methods: In this randomized clinical trial, 50 patients with NAFLD were randomly assigned to receive either cit. or placebo. Patients received four capsules of 500 mg (cit. or placebo) daily. Both groups were advised to follow energy-balanced diets and physical activities. Liver enzymes and hepatic steatosis and fibrosis were assessed at the baseline and end of the study. Paired t-test, t-test and chi-2 were used for data analysis.
Results: No significant differences were observed for the monitored variables between the two groups at the baseline. After treatment, the experimental group consuming cit. supplementation showed a statistically significant decrease for ALT and hepatic steatosis, compared to control group (P<0.05). Furthermore, serum levels of AST and GGT and also hepatic fibrosis showed no significant differences between the two groups (P≥0.05).
Conclusion: Results of this study showed that citrulline could decrease ALT and degrees of steatosis in cit. group with no significant differences between the two groups. In cit. group, liver enzymes of alanine aminotransferase  decreased (7.26 IU/L), compared to control group (7.19 IU/L). Moreover, citrulline demonstrated no significant effects on hepatic fibrosis and other liver enzymes. To investigated effects of citrulline on liver, further studies with various doses and periods of time are necessary.
Keywords: Non-alcoholic fatty liver disease, Citrulline, Liver enzyme, Hepatic steatosis
Full-Text [PDF 597 kb]   (664 Downloads)    
Type of Study: Research | Subject: nutrition
Received: 2018/11/8 | Accepted: 2019/02/1 | Published: 2019/10/7
1. Ouelaa W, Jegatheesan P, M'Bouyou-Boungou J, Vicente C, Nakib S, Nubret E, et al. Citrulline decreases hepatic endotoxin-induced injury in fructose-induced non-alcoholic liver disease: an ex vivo study in the isolated perfused rat liver. BJN. 2017;117(11):1487-94. [DOI:10.1017/S0007114517001453]
2. Sass DA, Chang P, Chopra KB. Nonalcoholic fatty liver disease: a clinical review. Digest Dis. Sci. 2005;50(1):171-80. [DOI:10.1007/s10620-005-1267-z]
3. Amoughli Tabrizi,d.Mohajeri.Preventive Effects of Green Tea Extractfrom Hepatic Steatosis in the Rats Fed with High Fat Diet. JRUMS. 2014;13(2):125_140. [in Persian]
4. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;482(7384):179-85. [DOI:10.1038/nature10809]
5. Lee BH, Jin HY, Kim GH, Choi JH, Yoo HW. Nonalcoholic fatty liver disease in 2 siblings with adult-onset type II citrullinemia. J Pediatr Gastroenterol Nutr. 2010;50(6):682- [DOI:10.1097/MPG.0b013e3181d67fbf]
6. Jegatheesan P, Beutheu S, Freese K, Waligora-Dupriet AJ, Nubret E, Butel MJ, et al. Preventive effects of citrulline on Western diet-induced non-alcoholic fatty liver disease in rats. BJN. 2016;116(2):191-203. [DOI:10.1017/S0007114516001793]
7. Volynets V, Kuper MA, Strahl S,.Maier IB, Spruss A, Wagnerberger S, et al. Nutrition, intestinal permeability, and blood ethanol levels are altered in patients with nonalcoholic fatty liver disease (NAFLD). Digest Dis. Sci. 2012;57(7):1932-41. [DOI:10.1007/s10620-012-2112-9]
8. Ashraf NU, Sheikh TA. Endoplasmic reticulum stress and Oxidative stress in the pathogenesis of Non-alcoholic fatty liver disease. Free Radic Res. 2015;49(12):1405-18. [DOI:10.3109/10715762.2015.1078461]
9. Al-Dayyat HM, Rayyan YM, Tayyem RF. Non-alcoholic fatty liver disease and associated dietary and lifestyle risk factors. Diabetes Metab Syndr. 2018;12(4):569-575. [DOI:10.1016/j.dsx.2018.03.016]
10. Comar K, Sterling R. drug therapy for non‐alcoholic fatty liver disease. Pharmacol. Ther. 2006;23(2):207-15. [DOI:10.1111/j.1365-2036.2006.02751.x]
11. Lindor KD, Kowdley KV, Heathcote EJ, Harrison ME, Jorgensen R, Angulo P, et al. Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial. Hepatology. 2004;39(3):770-8. [DOI:10.1002/hep.20092]
12. Hickman IJ, Jonsson JR, Prins JB, Ash S, Purdie DM, Clouston AD, et al. Modest weight loss and physical activity in overweight patients with chronic liver disease results in sustained improvements in alanine aminotransferase, fasting insulin, and quality of life. Gut. 2004;53(3):413-9. [DOI:10.1136/gut.2003.027581]
13. Kurauchi Y, Mokudai K, Mori A, Sakamoto K, Nakahara T, Morita M, et al. l-Citrulline ameliorates cerebral blood flow during cortical spreading depression in rats: Involvement of nitric oxide- and prostanoids-mediated pathway. Am. J. Pharmacol. Sci.2017;133(3):146-55. [DOI:10.1016/j.jphs.2017.02.004]
14. Orozco-Gutiérrez JJ, Castillo-Martínez L, Orea-Tejeda A, Vázquez-Díaz O, Valdespino-Trejo A, Narváez-David R, et al. Effect of L-arginine or L-citrulline oral supplementation on blood pressure and right ventricular function in heart failure patients with preserved ejection fraction. Cardiol. J. Cardiology journal .2010;17(6):612-8.
15. Osowska S, Duchemann T, Walrand S, Paillard A, Boirie Y, Cynober L, et al. Citrulline modulates muscle protein metabolism in old malnourished rats. Am J Physiol Endocrinol Metab. 2006;291(3):E582-E6. [DOI:10.1152/ajpendo.00398.2005]
16. Jegatheesan P, Beutheu S, Ventura G, Sarfati G, Nubret E, Kapel N, et al. Effect of specific amino acids on hepatic lipid metabolism in fructose-induced non-alcoholic fatty liver disease. Clin. Nutr. 2016;35(1):175-82. [DOI:10.1016/j.clnu.2015.01.021]
17. Moinard C, Le Plenier S, Noirez P, Morio B, Bonnefont-Rousselot D, Kharchi C, et al. Citrulline Supplementation Induces Changes in Body Composition and Limits Age-Related Metabolic Changes in Healthy Male Rats-3. Nutr. J. 2015;145(7):1429-37. [DOI:10.3945/jn.114.200626]
18. Eslamparast T, Poustchi H, Zamani F, Sharafkhah M, Malekzadeh R, Hekmatdoost A. Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled pilot study. AJCN .2014;99(3):535-42. [DOI:10.3945/ajcn.113.068890]
19. Aadahl M, Jorgensen T. Validation of a new self-report instrument for measuring physical activit. MSSE. 2003;35(7):1196-202. [DOI:10.1249/01.MSS.0000074446.02192.14]
20. Kelishadi R, Ardalan G, Gheiratmand R, Gouya MM, Razaghi EM, Delavari A, et al. Association of physical activity and dietary behaviours in relation to the body mass index in a national sample of Iranian children and adolescents: CASPIAN Study. Bull World Health Organ. 2007;85(1):19-26. [DOI:10.2471/BLT.06.030783]
21. Jegatheesan P, Beutheu S, Ventura G, Nubret E, Sarfati G, Bergheim I, et al. Citrulline and Nonessential Amino Acids Prevent Fructose-Induced Nonalcoholic Fatty Liver Disease in Rats. Nutr. J. 2015;145(10):2273-9. [DOI:10.3945/jn.115.218982]
22. Cuthbertson D. Citrulline: a new major signaling molecule or just another player in the pharmaconutrition game. Clin Nutr.29:545551.
23. Guo F, Cavener DR. The GCN2 eIF2α kinase regulates fatty-acid homeostasis in the liver during deprivation of an essential amino acid. CELL METAB. 2007;5(2):103-14. [DOI:10.1016/j.cmet.2007.01.001]
24. Joffin N, Jaubert A-M, Bamba J, Barouki R, Noirez P, Forest C. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats. ADIPOCYTE. 2015;4(2):129-34. [DOI:10.4161/21623945.2014.989748]
25. El‐Kirsh AAA, El‐Wahab A, Fathy HM, Sayed AE, Fahmy H. The effect of L‐arginine or L‐citrulline supplementation on biochemical parameters and the vascular aortic wall in high‐fat and high‐cholesterol‐fed rats. Cell Biochem. Funct. 2011;29(5):414. [DOI:10.1002/cbf.1766]
26. Sellmann C, Jin CJ, Engstler AJ, De Bandt J-P, Bergheim I. Oral citrulline supplementation protects female mice from the development of non-alcoholic fatty liver disease (NAFLD). Eur. J. Nutr.2017;56(8):2519-27. [DOI:10.1007/s00394-016-1287-9]
27. Malekzadeh R, Poustchi H. Fibroscan for assessing liver fibrosis: An acceptable alternative for liver biopsy: Fibroscan: an acceptable alternative for liver biopsy. Hepat. Mon. 2011;11(3):157-8.

XML   Persian Abstract   Print

Volume 14, Issue 3 (Autumn 2019) Back to browse issues page