Triple Therapy with Garlic, Silymarin and Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized, Placebo-Controlled Clinical Trial

  • Zahra Ataee Department of internal medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Maryam Vahabzadeh Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Seyedeh Shabnam Mazloumi Kiapey Department of Nutrition Science, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Hamid Reza Rahimi Vascular and Endovascular Surgery Research Center, Mashhad University of Medical Sciences, Mashhad, Iran Department of Medical Genetics and Molecular Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Department of Medical Genetics and Molecular Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Hooman Mosanan Mozaffari Gastroenterology and Hepatology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
  • Maliheh Ziaee * Department of Community Medicine, School of Medicine, Social Determinants of Health Research Center, Gonabad University of Medical Sciences, Gonabad, Iran
Keywords: NAFLD, Garlic, Silymarin, Curcumin, Liver


Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. We aimed to evaluate the effect of a mixture of garlic, silymarin, and curcumin on hepatic parameters and overall improvement of NAFLD. Materials and Methods: Individuals between 18 and 70 years of age with altered liver enzymes and confirmed pattern of fatty liver in their hepatic ultrasound were entered into this randomized, triple-blind, placebo-controlled trial and assigned to two groups. They received either capsules containing curcumin, silymarin and garlic or an identical placebo. After 3 months, the patients were re-evaluated for laboratory tests, clinical evaluation, and liver fibroscan. Data were analyzed in consistent with the intention-to-treat approach. Results: After randomization and blinding, 50 individuals entered this study. The mean age of the participants was 42.51 ± 11.13 (mean± SD) years of old, and 80% of the participants were men. After triple therapy, no significant differences were observed in laboratory tests between the two groups, except for the triglyceride level (188.86 ± 90.66 vs. 146.23 ± 70.38, p-value=0.04). However, hepatic fibroscans were noticeably ameliorated in the treatment group compared to the control (p-value <0.001). Conclusion: We observed no significant amelioration in the majority of biochemical indices of the patients, but patterns of NAFLD in fibroscans were considerably improved. Although we cannot entirely attribute this finding to our therapy with silymarin, curcumin, and garlic, a healthy lifestyle combined with these supplements can help improve the state of NAFLD. Further studies with larger sample size and different doses are recommended.


Jameson JL, Kaspe; DL, Longo DL. Harrison's principles of internal medicine 20th ed. New York: McGraw Hill Education; 2018.

Vahabzadeh M, Amiri N, Karimi G. Effects of silymarin on metabolic syndrome: a review. Journal of the Science of Food and Agriculture. 2018;98(13):4816-23.

Angulo P. Nonalcoholic fatty liver disease. New England Journal of Medicine. 2002;346(16):1221-31.

Chitturi S, Farrell GC, Hashimoto E, Saibara T, Lau GK, Sollano JD, et al. Non‐alcoholic fatty liver disease in the Asia–Pacific region: Definitions and overview of proposed guidelines. Journal of gastroenterology and hepatology. 2007;22(6):778-87.

Bedossa P, Dargère D, Paradis V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology. 2003;38(6):1449-57.

Capanni M, Calella F, Biagini M, Genise S, Raimondi L, Bedogni G, et al. Prolonged n‐3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non‐alcoholic fatty liver disease: a pilot study. Alimentary pharmacology & therapeutics. 2006;23(8):1143-51.

Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, et al. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Digestive and Liver Disease. 2008;40(3):194-9.

Cicero AF, Colletti A, Bellentani S. Nutraceutical approach to non-alcoholic fatty liver disease (NAFLD): the available clinical evidence. Nutrients. 2018;10(9):1153.

Karimi G, Vahabzadeh M, Lari P, Rashedinia M, Moshiri M. “Silymarin”, a promising pharmacological agent for treatment of diseases. Iranian journal of basic medical sciences. 2011;14(4):308.

Ki SH, Choi JH, Kim CW, Kim SG. Combined metadoxine and garlic oil treatment efficaciously abrogates alcoholic steatosis and CYP2E1 induction in rat liver with restoration of AMPK activity. Chemico-biological interactions. 2007;169(2):80-90.

Sangouni AA, Azar MRMH, Alizadeh M. Effects of garlic powder supplementation on insulin resistance, oxidative stress, and body composition in patients with non-alcoholic fatty liver disease: A randomized controlled clinical trial. Complementary Therapies in Medicine. 2020;51:102428.

Sun Y-E, Wang W, Qin J. Anti-hyperlipidemia of garlic by reducing the level of total cholesterol and low-density lipoprotein: A meta-analysis. Medicine. 2018;97(18).

Wei Z, Liu N, Tantai X, Xing X, Xiao C, Chen L, et al. The effects of curcumin on the metabolic parameters of non-alcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Hepatology international. 2019;13(3):302-13.

Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Blendis L, Halpern Z, et al. Long term nutritional intake and the risk for non-alcoholic fatty liver disease (NAFLD): a population based study. Journal of hepatology. 2007;47(5):711-7.

Zelber‐Sagi S, Nitzan‐Kaluski D, Goldsmith R, Webb M, Zvibel I, Goldiner I, et al. Role of leisure‐time physical activity in nonalcoholic fatty liver disease: a population‐based study. Hepatology. 2008;48(6):1791-8.

Zelber‐Sagi S, Nitzan‐Kaluski D, Halpern Z, Oren R. Prevalence of primary non‐alcoholic fatty liver disease in a population‐based study and its association with biochemical and anthropometric measures. Liver International. 2006;26(7):856-63.

Zhong S, Fan Y, Yan Q, Fan X, Wu B, Han Y, et al. The therapeutic effect of silymarin in the treatment of nonalcoholic fatty disease: A meta-analysis (PRISMA) of randomized control trials. Medicine. 2017;96(49).

Ried K, Toben C, Fakler P. Effect of garlic on serum lipids: an updated meta-analysis. Nutrition reviews. 2013;71(5):282-99.

Loguercio C, Andreone P, Brisc C, Brisc MC, Bugianesi E, Chiaramonte M, et al. Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial. Free Radical Biology and Medicine. 2012;52(9):1658-65.

Akhondi-Meybodi M, Baghbanian M, Namazi A. The Efficacy of Silymarin and Vitamin E in Non-Alcoholic Fatty Liver Disease: A Clinical Trial. Iranian journal of diabetes and obesity. 2020;12(2):84-9.

Solhi H, Ghahremani R, Kazemifar AM, Yazdi ZH. Silymarin in treatment of non-alcoholic steatohepatitis: A randomized clinical trial. Caspian journal of internal medicine. 2014;5(1):9.

Weaver L, Hamoud A-r, Stec DE, Hinds Jr TD. Biliverdin reductase and bilirubin in hepatic disease. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2018;314(6):G668-G76.

Barañano DE, Rao M, Ferris CD, Snyder SH. Biliverdin reductase: a major physiologic cytoprotectant. Proceedings of the national academy of sciences. 2002;99(25):16093-8.

Kwak M-S, Kim D, Chung GE, Kang SJ, Park MJ, Kim YJ, et al. Serum bilirubin levels are inversely associated with nonalcoholic fatty liver disease. Clinical and molecular hepatology. 2012;18(4):383.

Panahi Y, Kianpour P, Mohtashami R, Jafari R, Simental-Mendía LE, Sahebkar A. Curcumin lowers serum lipids and uric acid in subjects with nonalcoholic fatty liver disease: a randomized controlled trial. Journal of cardiovascular pharmacology. 2016;68(3):223-9.

Qamar A, Siddiqui A, Kumar H. Fresh garlic amelioration of high-fat-diet induced fatty liver in albino rats. Journal of the Pakistan Medical Association. 2015;65(10):1102-7.

Qamar A, Usmani A, Waqar H, Siddiqui A, Kumar H. Ameliorating effect of Allium Sativum on high-fat diet induced fatty liver in albino rats. Pakistan journal of medical sciences. 2016;32(2):403.

Seif El-Din SH, Sabra A-NA, Hammam OA, Ebeid FA, El-Lakkany NM. Pharmacological and antioxidant actions of garlic and/or onion in non-alcoholic fatty liver disease (NAFLD) in rats. Journal of the Egyptian Society of Parasitology. 2014;44(2):295-308.

Soleimani D, Paknahad Z, Askari G, Iraj B, Feizi A. Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Advanced biomedical research. 2016;5.

Kim H-N, Kang S-G, Roh YK, Choi M-K, Song S-W. Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: A double-blind, randomized, placebo-controlled trial. European journal of nutrition. 2017;56(5):1993-2002.

Zhang S, Gu Y, Wang L, Zhang Q, Liu L, Lu M, et al. Association between dietary raw garlic intake and newly diagnosed nonalcoholic fatty liver disease: a population-based study. European journal of endocrinology. 2019;181(6):591-602.

Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta‐analysis. Hepatology.2011;54(3):1082-90.

Original Article