Nonalcoholic fatty liver disease (NAFLD) begins with steatosis (accumulation of triglycerides in the liver) and can progress to steatohepatitis (NAFLD with inflammation and cell damage), fibrosis, cirrhosis, or hepatocellular carcinoma. No drug therapy has been approved to treat NAFLD, and dietary modification and exercise to reduce body weight are the only recommended treatments. Nigella (Nigella sativa, Ranunculaceae) seed oil (NSO) is used in Iranian traditional medicine to treat liver diseases. Experimental evidence suggests that NSO may reduce steatosis and improve lipid profiles and markers of liver function. However, clinical studies on NAFLD are lacking. Hence, the purpose of this randomized, double-blind, placebo-controlled study was to evaluate the efficacy of NSO in the treatment of NAFLD.

Patients (N = 120; mean age of 47 years) with NAFLD confirmed by ultrasonography participated in this study conducted at Baqiyatallah Hospital in Tehran, Iran. Excluded patients had a Child-Pugh score* greater than 7; hepatic disease other than NAFLD; were taking a drug that affects NAFLD; or were pregnant, planning pregnancy, or lactating.

Cold-pressed NSO was purchased from Barij Essence Pharmaceutical Company (Kashan, Iran). The thymoquinone and fatty acid content of the NSO were determined using high-performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. The NSO contained 0.987 ± 0.07 mg thymoquinone per mL. The main fatty acids were linoleic acid (49.37%), palmitic acid (20.27%), oleic acid (5.76%), stearic acid (5.48%), palmitoleic acid (0.94%), arachidic acid (0.90%), and myristic acid (0.63%).

Patients were randomly assigned to receive either 2.5 mL NSO (n = 60) or 2.5 mL mineral oil (placebo; n = 60). Both NSO and placebo were mixed with 1.25 mL honey and 1.25 mL water, and both were similar in appearance and smell. All patients were instructed to take 5 mL of the syrup every 12 hours for three months. The patients were asked not to make changes to their diet or physical activity over the course of the study. At baseline and at three months, ultrasonography was performed, and blood samples were drawn for analysis. The primary outcome measures were hepatic steatosis (graded via ultrasound) and serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). The secondary outcome measures were body mass index (BMI), complete blood cell count, and serum levels of high-density lipoprotein cholesterol (HDL-C), blood urea nitrogen, and creatinine.

There were no significant differences between groups at baseline. Compliance was good (patients took at least 80% of their assigned doses) in both groups. At baseline, no patients had fatty liver grade 0 (normal liver). However, at three months, 18 patients in the NSO group and four patients in the placebo group had fatty liver grade 0. Overall, the NSO group had a significant decrease in fatty liver grade compared with the placebo group (P < 0.01). ALT, AST, and TG levels significantly decreased and HDL-C levels significantly increased in the NSO group compared with the placebo group (P = 0.001 for all). There were no significant changes in the other measured parameters. No adverse events were reported.

In summary, three months of NSO supplementation improved liver steatosis, as well as liver aminotransferases, TG, and HDL-C levels in patients with NAFLD. The authors hypothesize that the reductions of hepatic steatosis and aminotransferases indicate that NSO may reverse hepatic injury and protect the liver in patients with NAFLD. Since there were no changes in body weight, the benefits of NSO were not due to weight loss. Acknowledged limitations of this study include the small sample size, short duration, and the lack of elastography, a type of medical imaging used to measure liver fibrosis. The authors concluded that larger, longer trials to evaluate NSO in the treatment of non-alcoholic steatohepatitis, hepatic fibrosis, and cirrhosis are warranted.

* The Child-Pugh score is a tool to assess the prognosis of chronic liver disease and cirrhosis.