The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Pakravan, Hassan; Ahmadian, Mehdi; Fani, Ali; Brumanad, Sareh; Pakzad, Bahram

The Effects of Melatonin in Patients with Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Authors

¹ Department of Internal Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

² Department of Gastroenterology, Isfahan University of Medical Sciences, Isfahan, Iran

³ Department of Internal Medicine, Arak University of Medical, Arak, Iran

⁴ Department of Radiology, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: This study was designed to evaluate the effect of melatonin on nonalcoholic fatty liver disease (NAFLD) in compared to placebo. Materials and Methods: A total of 100 patients with histopathological diagnosis NAFLD in two groups of case and control received oral melatonin or placebo thrice daily for 3 months. Collected data were weight, waist, systolic blood pressure (SBP), diastolic blood pressure (DBP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hsCRP), fatty liver grade, and side effects which were measured at baseline and after treatment period using standard clinical chemistry techniques. Results: Before treatment the mean of weight, waist, SBP, DBP, ALT, AST, and hsCRP between cases and controls were similar (P > 0.5). After treatment, only the differences in the mean of hsCRP in cases was significantly lower than controls (P = 0.003). In case group, all variables after treatment were significantly decreased compare to baseline (P > 0.5) and only AST after treatment was similar to before treatment (P > 0.5). The mean of a decrease in the level of weight, waist, SBP, and ALT were not statistically significant between groups (P > 0.5). In the case group in compare to control group the level of DBP, AST, and hsCRP significantly more decreased. After treatment fatty, liver grade was statistically improved in more cases than controls (P = 0.001). Side effects were similar between the two groups. Conclusion: Melatonin significantly decreases liver enzymes, so the use of melatonin in patients with NAFLD can be effective.

Keywords

References

1.	Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002;346:1221-31.
2.	Gonciarz M, Gonciarz Z, Bielanski W, Mularczyk A, Konturek PC, Brzozowski T, et al. The pilot study of 3-month course of melatonin treatment of patients with nonalcoholic steatohepatitis: Effect on plasma levels of liver enzymes, lipids and melatonin. J Physiol Pharmacol 2010;61:705-10.
3.	Ong JP, Younossi ZM. Epidemiology and natural history of NAFLD and NASH. Clin Liver Dis 2007;11:1-16, vii.
4.	Ascha MS, Hanouneh IA, Lopez R, Tamimi TA, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatology 2010;51:1972-8.
5.	Bedogni G, Miglioli L, Masutti F, Tiribelli C, Marchesini G, Bellentani S. Prevalence of and risk factors for nonalcoholic fatty liver disease: The dionysos nutrition and liver study. Hepatology 2005;42:44-52.
6.	Shen L, Fan JG, Shao Y, Zeng MD, Wang JR, Luo GH, et al. Prevalence of nonalcoholic fatty liver among administrative officers in Shanghai: An epidemiological survey. World J Gastroenterol 2003;9:1106-10.
7.	Omagari K, Kadokawa Y, Masuda J, Egawa I, Sawa T, Hazama H, et al. Fatty liver in non-alcoholic non-overweight Japanese adults: Incidence and clinical characteristics. J Gastroenterol Hepatol 2002;17:1098-105.
8.	Lai SW, Tan CK, Ng KC. Epidemiology of fatty liver in a hospital-based study in Taiwan. South Med J 2002;95:1288-92.
9.	Bosch FX, Ribes J, Díaz M, Cléries R. Primary liver cancer: Worldwide incidence and trends. Gastroenterology 2004;127 5 Suppl 1:S5-S16.
10.	Bellentani S, Scaglioni F, Marino M, Bedogni G. Epidemiology of non-alcoholic fatty liver disease. Dig Dis 2010;28:155-61.
11.	Berlanga A, Guiu-Jurado E, Porras JA, Auguet T. Molecular pathways in non-alcoholic fatty liver disease. Clin Exp Gastroenterol 2014;7:221-39.
12.	Zaitone S, Hassan N, El-Orabi N, El-Awady el-S. Pentoxifylline and melatonin in combination with pioglitazone ameliorate experimental non-alcoholic fatty liver disease. Eur J Pharmacol 2011;662:70-7.
13.	Dowman JK, Tomlinson JW, Newsome PN. Pathogenesis of non-alcoholic fatty liver disease. QJM 2010;103:71-83.
14.	Arendt BM, Allard JP. Effect of atorvastatin, Vitamin E and C on nonalcoholic fatty liver disease: Is the combination required? Am J Gastroenterol 2011;106:78-80.
15.	Duvnjak M, Tomasic V, Gomercic M, Smircic Duvnjak L, Barsic N, Lerotic I. Therapy of nonalcoholic fatty liver disease: Current status. J Physiol Pharmacol 2009;60 Suppl 7:57-66.
16.	Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, et al. Pioglitazone, Vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med 2010;362:1675-85.
17.	Rodriguez C, Mayo JC, Sainz RM, Antolín I, Herrera F, Martín V, et al. Regulation of antioxidant enzymes: A significant role for melatonin. J Pineal Res 2004;36:1-9.
18.	Tomás-Zapico C, Coto-Montes A. A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J Pineal Res 2005;39:99-104.
19.	Hatzis G, Ziakas P, Kavantzas N, Triantafyllou A, Sigalas P, Andreadou I, et al. Melatonin attenuates high fat diet-induced fatty liver disease in rats. World J Hepatol 2013;5:160-9.
20.	Hoyos M, Guerrero JM, Perez-Cano R, Olivan J, Fabiani F, Garcia-Pergañeda A, et al. Serum cholesterol and lipid peroxidation are decreased by melatonin in diet-induced hypercholesterolemic rats. J Pineal Res 2000;28:150-5.
21.	Sener G, Balkan J, Cevikbas U, Keyer-Uysal M, Uysal M. Melatonin reduces cholesterol accumulation and prooxidant state induced by high cholesterol diet in the plasma, the liver and probably in the aorta of C57BL/6J mice. J Pineal Res 2004;36:212-6.
22.	Pagadala M, Zein CO, McCullough AJ. Predictors of steatohepatitis and advanced fibrosis in non-alcoholic fatty liver disease. Clin Liver Dis 2009;13:591-606.
23.	Gonciarz M, Gonciarz Z, Bielanski W, Mularczyk A, Konturek PC, Brzozowski T, et al. The effects of long-term melatonin treatment on plasma liver enzymes levels and plasma concentrations of lipids and melatonin in patients with nonalcoholic steatohepatitis: A pilot study. J Physiol Pharmacol 2012;63:35-40.
24.	Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, et al. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: A randomized, controlled trial. Hepatology 2008;48:119-28.
25.	Promrat K, Kleiner DE, Niemeier HM, Jackvony E, Kearns M, Wands JR, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis. Hepatology 2010;51:121-9.
26.	Pan M, Song YL, Xu JM, Gan HZ. Melatonin ameliorates nonalcoholic fatty liver induced by high-fat diet in rats. J Pineal Res 2006;41:79-84.
27.	Sewerynek E, Reiter RJ, Melchiorri D, Ortiz GG, Lewinski A. Oxidative damage in the liver induced by ischemia-reperfusion: Protection by melatonin. Hepatogastroenterology 1996;43:898-905.
28.	Celinski K, Konturek PC, Slomka M, Cichoz-Lach H, Brzozowski T, Konturek SJ, et al. Effects of treatment with melatonin and tryptophan on liver enzymes, parameters of fat metabolism and plasma levels of cytokines in patients with non-alcoholic fatty liver disease – 14 months follow up. J Physiol Pharmacol 2014;65:75-82.

Advanced Biomedical Research