Nigella sativa supplementation and non-alcoholic fatty liver disease: A systematic review of clinical trials

Objective: Based on the results of previous studies, the effects of N. sativa on some of the non-alcoholic fatty liver disease's (NAFLD) biomarkers were positive; however, there were conflicting results regarding other variables. Therefore, the present systematic review of clinical trials was designed to clarify whether N. sativa effectively prevents the progression of NAFLD. Materials and Methods: A search of four databases (Scopus, PubMed, Medline, and Google scholar) was conducted to identify the clinical trials that assessed the effects of N. sativa supplementation on NAFLD. The outcome variables of interest were biomarkers of hepatic steatosis, liver enzymes, insulin resistance, and inflammation. Results: Overall, four randomized clinical trials (RCTs) were included. In three studies, hepatic steatosis grade decreased significantly after N. sativa supplementation. Serum levels of liver enzymes reduced significantly in three of four included trials. In the only study that examined the effect of N. sativa on insulin resistance parameters, all variables related to this factor were significantly reduced. In two included studies that measured biomarkers of inflammation, the serum levels of tumor necrosis factor α (TNF-α), high-sensitive C-reactive protein (hs-CRP), and interleukin 6 (IL-6) decreased significantly after intaking N. sativa supplements. Conclusion: Although the efficacy of N. sativa on liver enzymes and the grade of hepatic steatosis was reported in some of the included studies, more well-designed clinical trials are needed to determine the definitive effects of N. sativa on NAFLD. The present study provides suggestions that help to design future studies in this field.

[1]  M. Farag,et al.  MUFA in metabolic syndrome and associated risk factors: is MUFA the opposite side of the PUFA coin? , 2021, Food & function.

[2]  Hafiz Ansar Rasul Suleria,et al.  Nigella Plants – Traditional Uses, Bioactive Phytoconstituents, Preclinical and Clinical Studies , 2021, Frontiers in Pharmacology.

[3]  J. Tao,et al.  Effect of Nigella sativa in the treatment of nonalcoholic fatty liver disease: A systematic review and meta‐analysis of randomized controlled trials , 2021, Phytotherapy research : PTR.

[4]  Ali-asghar Ebrahimi,et al.  Effect of Nigella sativa oil extracts on inflammatory and oxidative stress markers in Behcet’s disease: A randomized, double-blind, placebo-controlled clinical trial , 2020, Avicenna journal of phytomedicine.

[5]  A. Maamri,et al.  Herbal Medicine in Chronic Diseases Treatment: Determinants, Benefits and Risks , 2020 .

[6]  M. Mohammadshahi,et al.  The effect of Nigella sativa oil on serum levels of inflammatory markers, liver enzymes, lipid profile, insulin and fasting blood sugar in patients with non-alcoholic fatty liver , 2019, Journal of Diabetes & Metabolic Disorders.

[7]  S. Alavian,et al.  The effects of black seed supplementation on cardiovascular risk factors in patients with nonalcoholic fatty liver disease: A randomized, double‐blind, placebo‐controlled clinical trial , 2019, Phytotherapy research : PTR.

[8]  Natalie S Blencowe,et al.  RoB 2: a revised tool for assessing risk of bias in randomised trials , 2019, BMJ.

[9]  S. Alavian,et al.  Nigella sativa and inflammatory biomarkers in patients with non-alcoholic fatty liver disease: Results from a randomized, double-blind, placebo-controlled, clinical trial. , 2019, Complementary therapies in medicine.

[10]  R. Mohtashami,et al.  Standardized Nigella sativa seed oil ameliorates hepatic steatosis, aminotransferase and lipid levels in non-alcoholic fatty liver disease: A randomized, double-blind and placebo-controlled clinical trial. , 2019, Journal of ethnopharmacology.

[11]  N. Sharifi,et al.  Vitamin D supplementation and non-alcoholic fatty liver disease: A critical and systematic review of clinical trials , 2019, Critical reviews in food science and nutrition.

[12]  G. Marchesini,et al.  Epidemiology of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: Implications for Liver Transplantation. , 2019, Transplantation.

[13]  Z. Younossi,et al.  Advances and challenges in the management of advanced fibrosis in nonalcoholic steatohepatitis , 2018, Therapeutic advances in gastroenterology.

[14]  M. Abdellaoui,et al.  Ameliorating effects of Nigella sativa oil on aggravation of inflammation, oxidative stress and cytotoxicity induced by smokeless tobacco extract in an allergic asthma model in Wistar rats. , 2018, Allergologia et immunopathologia.

[15]  S. Bellentani,et al.  Nutraceutical Approach to Non-Alcoholic Fatty Liver Disease (NAFLD): The Available Clinical Evidence , 2018, Nutrients.

[16]  K. Freitas,et al.  An Overview of Novel Dietary Supplements and Food Ingredients in Patients with Metabolic Syndrome and Non-Alcoholic Fatty Liver Disease , 2018, Molecules.

[17]  M. Nematy,et al.  Efficacy of Black Seed ( Nigella sativa ) and Lemon Balm ( Melissa officinalis ) on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Clinical Trial , 2018 .

[18]  E. Chartampilas Imaging of nonalcoholic fatty liver disease and its clinical utility , 2018, Hormones.

[19]  A. McCullough,et al.  The Natural History of Nonalcoholic Fatty Liver Disease-An Evolving View. , 2018, Clinics in liver disease.

[20]  M. Khazaei,et al.  Renoprotective effect of Nigella sativa against cisplatin-induced nephrotoxicity and oxidative stress in rat. , 2018, Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia.

[21]  C. Gandhi Hepatic stellate cell activation and pro-fibrogenic signals. , 2017, Journal of hepatology.

[22]  M. Khazaei,et al.  Thymoquinone restores liver fibrosis and improves oxidative stress status in a lipopolysaccharide-induced inflammation model in rats , 2017, Avicenna journal of phytomedicine.

[23]  Chandragouda R. Patil,et al.  Therapeutic Potential and Pharmaceutical Development of Thymoquinone: A Multitargeted Molecule of Natural Origin , 2017, Front. Pharmacol..

[24]  M. Hussain,et al.  Effects of nigella sativa on various parameters in Patients of non-alcoholic fatty liver disease. , 2017, Journal of Ayub Medical College, Abbottabad : JAMC.

[25]  M. Balbaa,et al.  Oxidative stress and expression of insulin signaling proteins in the brain of diabetic rats: Role of Nigella sativa oil and antidiabetic drugs , 2017, PloS one.

[26]  A. Hekmatdoost,et al.  Nonalcoholic Fatty Liver Disease, the Gut Microbiome, and Diet. , 2017, Advances in nutrition.

[27]  G. Parati,et al.  A systematic review and meta-analysis of randomized controlled trials investigating the effects of supplementation with Nigella sativa (black seed) on blood pressure , 2016, Journal of hypertension.

[28]  C. Mantzoros,et al.  Non-alcoholic fatty liver disease and dyslipidemia: An update. , 2016, Metabolism: clinical and experimental.

[29]  M. Heydari,et al.  Efficacy of the Hydroalcoholic Extract of Tribulus terrestris on the Serum Glucose and Lipid Profile of Women With Diabetes Mellitus , 2016, Journal of evidence-based complementary & alternative medicine.

[30]  L. Wood,et al.  Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: A randomized controlled clinical trial. , 2016, Complementary therapies in clinical practice.

[31]  S. Kheirouri,et al.  Effects of Nigella sativa oil extract on inflammatory cytokine response and oxidative stress status in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled clinical trial , 2016, Avicenna journal of phytomedicine.

[32]  M. Mahmoudabady,et al.  The effects of hydroalcoholic extract of Nigella sativa seed on oxidative stress in hippocampus of STZ-induced diabetic rats , 2015, Avicenna journal of phytomedicine.

[33]  Jianpin Liu,et al.  Chinese Herbal Medicine Combined with Conventional Therapy for Blood Pressure Variability in Hypertension Patients: A Systematic Review of Randomized Controlled Trials , 2015, Evidence-based complementary and alternative medicine : eCAM.

[34]  A. Hosseinzadeh Colagar,et al.  Thymoquinone and its therapeutic potentials. , 2015, Pharmacological research.

[35]  A. Naveed,et al.  Comparative evaluation of Nigella sativa (Kalonji) and simvastatin for the treatment of hyperlipidemia and in the induction of hepatotoxicity. , 2015, Pakistan journal of pharmaceutical sciences.

[36]  N. Sharifi,et al.  Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial , 2014, Endocrine.

[37]  J. Nan,et al.  Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1-AMPK signaling pathway in mice. , 2014, International immunopharmacology.

[38]  M. Ermani,et al.  Ambulatory arterial stiffness indices and non-alcoholic fatty liver disease in essential hypertension. , 2013, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[39]  H. Tilg,et al.  Adiponectin: key player in the adipose tissue-liver crosstalk. , 2012, Current medicinal chemistry.

[40]  C. Borghi,et al.  Effect of a combined nutraceutical containing Orthosiphon stamineus effect on blood pressure and metabolic syndrome components in hypertensive dyslipidaemic patients: a randomized clinical trial. , 2012, Complementary therapies in clinical practice.

[41]  N. Johnson,et al.  Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. , 2012, Journal of hepatology.

[42]  F. Tanfani,et al.  Characterization of thymoquinone binding to human α₁-acid glycoprotein. , 2012, Journal of pharmaceutical sciences.

[43]  J. Chan,et al.  A systematic review on use of Chinese medicine and acupuncture for treatment of obesity , 2012, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[44]  J. Hardies,et al.  Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease , 2012, Hepatology.

[45]  E. Mohammadi,et al.  Barriers and facilitators related to the implementation of a physiological track and trigger system: A systematic review of the qualitative evidence , 2017, International journal for quality in health care : journal of the International Society for Quality in Health Care.

[46]  A. López-Suárez,et al.  Nonalcoholic fatty liver disease is associated with blood pressure in hypertensive and nonhypertensive individuals from the general population with normal levels of alanine aminotransferase , 2011, European journal of gastroenterology & hepatology.

[47]  P. Haddad,et al.  The In Vivo Antidiabetic Activity of Nigella sativa Is Mediated through Activation of the AMPK Pathway and Increased Muscle Glut4 Content , 2011, Evidence-based complementary and alternative medicine : eCAM.

[48]  P. Newsome,et al.  Systematic review: the diagnosis and staging of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis , 2010, Alimentary pharmacology & therapeutics.

[49]  B. Larijani,et al.  The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. , 2010, Current pharmaceutical design.

[50]  J. Vieira,et al.  Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals. , 2010, Arquivos de gastroenterologia.

[51]  E. Jackvony,et al.  Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis , 2010, Hepatology.

[52]  N. Ismail,et al.  Antioxidant activity and phenolic content of phenolic rich fractions obtained from black cumin (Nigella sativa) seedcake. , 2009 .

[53]  S. Caldwell,et al.  Systematic review of risk factors for fibrosis progression in non-alcoholic steatohepatitis. , 2009, Journal of hepatology.

[54]  B. Larijani,et al.  A systematic review of the efficacy and safety of herbal medicines used in the treatment of obesity. , 2009, World journal of gastroenterology.

[55]  M. Ismail,et al.  Regulation of Apolipoprotein A-1 and Apolipoprotein B100 Genes by Thymoquinone Rich Fraction and Thymoquinone in HEPG2 Cells. , 2009 .

[56]  L. Sechi,et al.  Nonalcoholic fatty liver disease, adiponectin and insulin resistance in dipper and nondipper essential hypertensive patients , 2008, Journal of hypertension.

[57]  M. Canela,et al.  Phytosterols: physiologic and metabolic aspects related to cholesterol-lowering properties. , 2008, Nutrition research.

[58]  G. Stephanopoulos,et al.  Hepatic insulin resistance is sufficient to produce dyslipidemia and susceptibility to atherosclerosis. , 2008, Cell metabolism.

[59]  H. Saleh,et al.  Liver biopsy remains the gold standard for evaluation of chronic hepatitis and fibrosis. , 2007, Journal of gastrointestinal and liver diseases : JGLD.

[60]  Anne L Hume,et al.  Complementary and alternative medicine. , 2007, American journal of pharmaceutical education.

[61]  M. Sayed-Ahmed,et al.  THYMOQUINONE SUPPLEMENTATION PREVENTS THE DEVELOPMENT OF GENTAMICIN‐INDUCED ACUTE RENAL TOXICITY IN RATS , 2007, Clinical and experimental pharmacology & physiology.

[62]  Tetsuji Sato,et al.  The metabolic syndrome as a predictor of nonalcoholic fatty liver disease. , 2006, Annals of internal medicine.

[63]  M. Salem Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. , 2005, International immunopharmacology.

[64]  H. Minuk,et al.  Metabolic syndrome. , 2005, Journal of insurance medicine.

[65]  D. Altman,et al.  Measuring inconsistency in meta-analyses , 2003, BMJ : British Medical Journal.

[66]  T. Kaptchuk,et al.  Systematic review of herbs and dietary supplements for glycemic control in diabetes. , 2003, Diabetes care.

[67]  G. Pacini,et al.  Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: Further evidence for an etiologic association , 2002, Hepatology.

[68]  V. Janout,et al.  Detection of insulin resistance by simple quantitative insulin sensitivity check index QUICKI for epidemiological assessment and prevention. , 2002, The Journal of clinical endocrinology and metabolism.

[69]  M. Drumm in vivo. , 1999 .