Drug Res (Stuttg) 2017; 67(04): 244-251
DOI: 10.1055/s-0043-100019
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Efficacy and Safety of Phytosomal Curcumin in Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Trial

Yunes Panahi
1   Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Parisa Kianpour
2   Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Reza Mohtashami
3   Religion and Medicine Research Center, Baqiyatallah University of Medical Sciences, Mashhad, Iran
Ramezan Jafari
4   Baqiyatallah University of Medical Sciences, Mashhad, Iran
Luis E. Simental-Mendía
5   Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico
Amirhossein Sahebkar
6   Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
7   Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
› Author Affiliations
Further Information

Publication History

received 05 November 2016

accepted 22 December 2016

Publication Date:
03 February 2017 (online)



Non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by excess lipid deposition in the hepatic tissue and subsequent oxidative and inflammatory damage. Curcumin is a dietary polyphenol with lipid-modifying, antioxidant and anti-inflammatory properties. This study aimed to evaluate the efficacy and safety of supplementation with phytosomal curcumin in subjects with NAFLD.


Patients diagnosed with NAFLD (grades 1–3 according to liver ultrasonography) were randomly assigned to the curcumin (phytosomal form; 1 000 mg/day in 2 divided doses) (n=50) or placebo group (n=52) for a period of 8 weeks. All patients received dietary and lifestyle advises before the start of trial. Anthropometric measurements, hepatic enzymes, and liver ultrasonography were assessed at baseline and after 8 weeks of follow-up.


87 subjects (n=44 and 43 in the curcumin and control group, respectively) completed the trial. Supplementation with curcumin was associated with a reduction in body mass index (−0.99±1.25 vs.  − 0.15±1.31 in the curcumin and placebo groups, respectively; p=0.003) and waist circumference (−1.74±2.58 vs. −0.23±3.49 in the curcumin and placebo groups, respectively; p=0.024). Ultrasonographic findings were improved in 75.0% of subjects in the curcumin group, while the rate of improvement in the control group was 4.7% (p<0.001). Serum levels of aspartate aminotransferase and alanine aminotransferase were reduced by the end of trial in the curcumin group (p<0.001) but elevated in the control group (p<0.001). Curcumin was safe and well tolerated during the course of trial.


Short-term supplementation with curcumin improves liver fat and transaminase levels in patients with NAFLD.

  • References

  • 1 Williamson RM, Price JF, Glancy S. et al. Prevalence of and risk factors for hepatic steatosis and nonalcoholic Fatty liver disease in people with type 2 diabetes: the Edinburgh Type 2 Diabetes Study. Diabetes Care 2011; 34: 1139-1144 doi:10.2337/dc10-2229
  • 2 Clark JM, Diehl AM. Hepatic steatosis and type 2 diabetes mellitus. Curr Diab Rep 2002; 2: 210-215
  • 3 Bedogni G, Miglioli L, Masutti F. et al. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. Hepatology 2005; 42: 44-52
  • 4 Browning JD, Szczepaniak LS, Dobbins R. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-1395
  • 5 Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 2011; 34: 274-285 doi:10.1111/j.1365-2036.2011.04724.x
  • 6 Solga SF, Diehl AM. Gut flora-based therapy in liver disease? The liver cares about the gut. Hepatology 2004; 39: 1197-1200
  • 7 Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006; 43: S99-S112
  • 8 Adams LA, Lymp St JF, Sauver J. et al. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129: 113-121
  • 9 Day CP, James OF. Steatohepatitis: a tale of two “hits”?. Gastroenterology 1998; 114: 842-845
  • 10 Gupta SC, Kismali G, Aggarwal BB. Curcumin, a component of turmeric: from farm to pharmacy. Biofactors 2013; 39: 2-13 doi:10.1002/biof.1079
  • 11 Oetari S, Sudibyo M, Commandeur JN. et al. Effects of curcumin on cytochrome P450 and glutathione S-transferase activities in rat liver. Biochem Pharmacol 1996; 51: 39-45
  • 12 Huang MT, Lysz T, Ferraro T. et al. Inhibitory effects of curcumin on in vitro lipoxygenase and cyclooxygenase activities in mouse epidermis. Cancer Res 1991; 51: 813-819
  • 13 Rao CV, Rivenson A, Simi B. et al. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res 1995; 55: 259-266
  • 14 Panahi Y, Ghanei M, Bashiri S. et al. Short-term curcuminoid supplementation for chronic pulmonary complications due to sulfur mustard intoxication: positive results of a randomized double-blind placebo-controlled Trial. Drug Res (Stuttg) 2015; 65: 567-573 doi:10.1055/s-0034-1389986
  • 15 Sahebkar A. Why it is necessary to translate curcumin into clinical practice for the prevention and treatment of metabolic syndrome?. Biofactors 2013; 39: 197-208 doi:10.1002/biof.1062
  • 16 Panahi Y, Hosseini MS, Khalili N. et al. Antioxidant and anti-inflammatory effects of curcuminoid-piperine combination in subjects with metabolic syndrome: A randomized controlled trial and an updated meta-analysis. Clin Nutr 2015; 34: 1101-1108 doi:10.1016/j.clnu.2014.12.019
  • 17 Panahi Y, Saadat A, Beiraghdar F. et al. Adjuvant therapy with bioavailability-boosted curcuminoids suppresses systemic inflammation and improves quality of life in patients with solid tumors: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28: 1461-1467 doi:10.1002/ptr.5149
  • 18 Panahi Y, Sahebkar A, Parvin S. et al. A randomized controlled trial on the anti-inflammatory effects of curcumin in patients with chronic sulphur mustard-induced cutaneous complications. Ann Clin Biochem 2012; 49: 580-588 doi:10.1258/acb.2012.012040
  • 19 Panahi Y, Rahimnia AR, Sharafi M. et al. Curcuminoid treatment for knee osteoarthritis: a randomized double-blind placebo-controlled trial. Phytother Res 2014; 28: 1625-1631 doi:10.1002/ptr.5174
  • 20 Esmaily H, Sahebkar A, Iranshahi M. et al. An investigation of the effects of curcumin on anxiety and depression in obese individuals: A randomized controlled trial. Chin J Integr Med 2015; 21: 332-338 doi:10.1007/s11655-015-2160-z
  • 21 Panahi Y, Badeli R, Karami GR. et al. Investigation of the efficacy of adjunctive therapy with bioavailability-boosted curcuminoids in major depressive disorder. Phytother Res 2015; 29: 17-21 doi:10.1002/ptr.5211
  • 22 Zabihi NA, Pirro M, Johnston TP et al. Is there a role for curcumin supplementation in the treatment of non-alcoholic fatty liver disease? The data suggest yes. Curr Pharm Des 2016 [Epub ahead of print] PubMed PMID:27748192
  • 23 Khonche A, Biglarian O, Panahi Y. et al. Adjunctive therapy with curcumin for peptic ulcer: a randomized controlled trial. Drug Res (Stuttg) 2016; 66: 444-448
  • 24 Shehzad A, Lee YS. Curcumin multiple molecular targets mediate multiple pharmacological actions - A review. Drugs Future 2010; 35: 113-119
  • 25 Ghandadi M, Sahebkar A. Curcumin: An effective inhibitor of interleukin-6. Curr Pharm Des 2016 [Epub ahead of print] PubMed PMID: 27719643
  • 26 Karimian MS, Pirro M, Majeed M. et al. Curcumin as a natural regulator of monocyte chemoattractant protein-1. Cytokine Growth Factor Rev. 2016; pii: S1359-6101(16)30131-9 DOI: 10.1016/j.cytogfr.2016.10.001.
  • 27 Panahi Y, Hosseini MS, Khalili N. et al. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial. Biomed Pharmacother 2016; 82: 578-582 doi:10.1016/j.biopha.2016.05.037
  • 28 Sahebkar A, Cicero AF, Simental-Mendía LE. et al. Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res 2016; 107: 234-242 doi: doi:10.1016/j.phrs.2016.03.026 Review
  • 29 Momtazi AA, Shahabipour F, Khatibi S. et al. Curcumin as a MicroRNA regulator in cancer: a review. Rev Physiol Biochem Pharmacol 2016; 171: 1-38
  • 30 Na LX, Li Y, Pan HZ. et al. Curcuminoids exert glucose-lowering effect in type 2 diabetes by decreasing serum free fatty acids: a double-blind, placebo-controlled trial. Mol Nutr Food Res 2013; 57: 1569-1577 doi:10.1002/mnfr.201200131
  • 31 Chuengsamarn S, Rattanamongkolgul S, Luechapudiporn R. et al. Curcumin extract for prevention of type 2 diabetes. Diabetes Care 2012; 35: 2121-2127 doi:10.2337/dc12-0116
  • 32 Ramirez-Tortosa MC, Ramirez-Tortosa CL, Mesa MD. et al. Curcumin ameliorates rabbits’s steatohepatitis via respiratory chain, oxidative stress, and TNF-alpha. Free Radic Biol Med 2009; 47: 924-931
  • 33 Bradford PG. Curcumin and obesity. Biofactors 2013; 39: 78-87 doi:10.1002/biof.1074
  • 34 Panahi Y, Sahebkar A, Amiri M. et al. Improvement of sulphur mustard-induced chronic pruritus, quality of life and antioxidant status by curcumin: results of a randomised, double-blind, placebo-controlled trial. Br J Nutr 2012; 108: 1272-1279
  • 35 Sahebkar A. Are curcuminoids effective C-reactive protein-lowering agents in clinical practice? Evidence from a meta-analysis. Phytother Res 2014; 28: 633-642 doi:10.1002/ptr.5045
  • 36 Kang HC, Nan JX, Park PH. et al. Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro. Journal of Pharmacy and Pharmacology 2002; 54: 119-126
  • 37 Sahebkar A, Mohammadi A, Atabati A. et al. Curcuminoids modulate pro-oxidant-antioxidant balance but not the immune response to heat shock protein 27 and oxidized LDL in obese individuals. Phytother Res 2013; 27: 1883-1888 doi:10.1002/ptr.4952
  • 38 Panahi Y, Alishiri GH, Parvin S. et al. Mitigation of systemic oxidative stress by curcuminoids in osteoarthritis: results of a randomized Controlled Trial. J Diet Suppl 2016; 13: 209-220 doi:10.3109/19390211.2015.1008611
  • 39 Panahi Y, Ghanei M, Hajhashemi A. et al. Effects of curcuminoids-piperine combination on systemic oxidative stress, clinical symptoms and quality of life in subjects with chronic pulmonary complications due to sulfur mustard: A randomized controlled trial. J Diet Suppl 2016; 13: 93-105 doi:10.3109/19390211.2014.952865
  • 40 Hasan ST, Zingg JM, Kwan P. et al. Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice. Atherosclerosis 2014; 232: 40-51
  • 41 Öner-İyidoğan Y, Koçak H, Seyidhanoğlu M. et al. Curcumin prevents liver fat accumulation and serum fetuin-A increase in rats fed a high-fat diet. J Physiol Biochem 2013; 69: 677-686
  • 42 Mohammadi A, Sahebkar A, Iranshahi M. et al. Effects of supplementation with curcuminoids on dyslipidemia in obese patients: a randomized crossover trial. Phytother Res 2013; 27: 374-379 doi:10.1002/ptr.4715
  • 43 Sahebkar A. Curcuminoids for the management of hypertriglyceridaemia. Nat Rev Cardiol 2014; 11: 123 doi:10.1038/nrcardio.2013.140-c1
  • 44 Sahebkar A. Low-density lipoprotein is a potential target for curcumin: novel mechanistic insights. Basic & Clinical Pharmacology & Toxicology 2014; 114: 437-438 doi:10.1111/bcpt.12212
  • 45 Panahi Y, Khalili N, Hosseini MS. et al. Lipid-modifying effects of adjunctive therapy with curcuminoids-piperine combination in patients with metabolic syndrome: results of a randomized controlled trial. Complement Ther Med 2014; 22: 851-857 doi:10.1016/j.ctim.2014.07.006
  • 46 Sahebkar A, Chew GT, Watts GF. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog Lipid Res 2014; 56: 47-66 doi:10.1016/j.plipres.2014.07.002
  • 47 Semalty A, Semalty M, Rawat MS. et al. Supramolecular phospholipids-polyphenolics interactions: the PHYTOSOME strategy to improve the bioavailability of phytochemicals. Fitoterapia 2010; 81: 306-314 doi:10.1016/j.fitote.2009.11.001
  • 48 Um MY, Hwang KH, Ahn J. et al. Curcumin attenuates diet-induced hepatic steatosis by activating AMP-activated protein kinase. Basic Clin Pharmacol Toxicol 2013; 113: 152-157 doi:10.1111/bcpt.12076
  • 49 Aggarwal BB. Targeting inflammation-induced obesity and metabolic diseases by curcumin and other nutraceuticals. Annu Rev Nutr 2010; 30: 173-199 doi:10.1146/annurev.nutr.012809.104755
  • 50 Vizzutti F, Provenzano A, Galastri S. et al. Curcumin limits the fibrogenic evolution of experimental steatohepatitis. Lab Invest 2010; 90: 104-115 doi:10.1038/labinvest.2009.112
  • 51 Tang Y, Zheng S, Chen A. Curcumin eliminates leptin’s effects on hepatic stellate cell activation via interrupting leptin signaling. Endocrinology 2009; 150: 3011-3020 10.1210/en.2008-1601
  • 52 Nanji AA, Jokelainen K, Rahemtulla A. et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat. Hepatology 1999; 30: 934-943
  • 53 Nabavi SF, Eslami S, Moghaddam AH. et al. Protective effects of curcumin against fluoride-induced oxidative stress in the rat brain. Neurophysiology 2011; 43: 287-291
  • 54 Nabavi SF, Nabavi SM, Abolhasani F. et al. Cytoprotective effects of curcumin on sodium fluoride-induced intoxication in rat erythrocytes. Bull Environ Contam Toxicol 2012; 88: 486-490 doi:10.1007/s00128-011-0495-5
  • 55 Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 2010; 5: 145-171 doi:10.1146/annurev-pathol-121808-102132
  • 56 Brunt EM. Pathology of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 2010; 7: 195-203 doi:10.1038/nrgastro.2010.21
  • 57 Brunt EM. Histological assessment of nonalcoholic fatty liver disease in adults and children. Clin Liver Dis 2012; 1: 107-110
  • 58 Puri P, Sanyal AJ. Nonalcoholic fatty liver disease: definitions, risk factors, and workup. Clin Liver Dis 2012; 1: 98-102
  • 59 Ramirez-Tortosa MC, Ramirez-Tortosa CL, Mesa MD. et al. Curcumin ameliorates rabbits’s steatohepatitis via respiratory chain, oxidative stress, and TNF-alpha. Free Radic Biol Med 2009; 47: 924-931 doi:10.1016/j.freeradbiomed.2009.06.015
  • 60 Leclercq IA, Farrell GC, Sempoux C. et al. Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice. J Hepatol 2004; 41: 926-934
  • 61 Wang Y, Li J, Zhuge L. et al. Comparison between the efficacies of curcumin and puerarin in C57BL/6 mice with steatohepatitis induced by a methionine- and choline-deficient diet. Exp Ther Med 2014; 7: 663-668
  • 62 Nseir W, Hellou E, Assy N. Role of diet and lifestyle changes in nonalcoholic fatty liver disease. World J Gastroenterol 2014; 20: 9338-9344
  • 63 Finelli C, Tarantino G. Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?. World J Gastroenterol 2012; 18: 6790-6800 doi:10.3748/wjg.v18.i46.6790
  • 64 Huang WC, Chiu WC, Chuang HL. et al. Effect of curcumin supplementation of physiological fatigue and physical performance in mice. Nutrients 2015; 7: 905-921
  • 65 Nabavi SF, Daglia M, Moghaddam AH. et al. Curcumin and liver disease: from chemistry to medicine. Comprehensive Reviews in Food Science and Food Safety. 2014; 13: 62-77 doi:10.1111/1541-4337.12047
  • 66 Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol 2008; 75: 787-809
  • 67 Hatcher H, Planalp R, Cho J. et al. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci 2008; 65: 1631-1652 doi:10.1007/s00018-008-7452-4
  • 68 Soni KB, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers. Indian J Physiol Pharmacol 1992; 36: 273-275
  • 69 Osawa H, Mori Y. Sonographic diagnosis of fatty liver using a histogram technique that compares liver and renal cortical echo amplitudes. J Clin Ultrasound 1996; 24: 25-29
  • 70 Hernaez R, Lazo M, Bonekamp S. et al. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology 2011; 54: 1082-1090 doi:10.1002/hep.24452