Artichoke Leaf Extract Improves Liver Disease Parameters in Patients with Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), the most common cause of chronic liver disease, is associated with metabolic syndrome. It can progress to cirrhosis and hepatocellular carcinoma; however, the progression is potentially reversible. The few therapeutic agents approved to treat the disease are not always successful. Some studies suggest that for people with the disease, dietary modifications of macronutrients and micronutrients and the use of phytochemicals can be beneficial. Artichoke (Cynara cardunculus Scolymus Group, Asteraceae) leaf extract (ALE) has shown potential as a lipid-lowering and hepatoprotective agent because of its component antioxidants, sesquiterpenes, and flavonoids.

These authors previously conducted a systematic review and meta-analysis of the literature on the lipid-lowering effects of artichoke extracts.They concluded that in patients with mild-to-moderate hypercholesterolemia, the consumption of artichoke extract significantly reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), and triglycerides but did not affect high-density lipoprotein cholesterol (HDL-C). The effects appeared to be related to baseline LDL-C levels and not to the dose or duration of treatment.

The authors conducted this randomized, double-blind, controlled pilot study to determine the efficacy of ALE in the treatment of NAFLD. Included in the study were adults aged 18 years and older who were referred to the Gastroenterology and Hepatology Clinic of Baqiyatallah Hospital in Tehran, Iran, with hepatic steatosis (grade 1-3) diagnosed by liver ultrasonography. The patients were randomly assigned to take one 200 mg Cynarol (Niak Pharmaceuticals; Gorgan, Iran) tablet (n=50) or placebo (n=50) every eight hours daily for two months. Each Cynarol tablet contained dried ALE standardized to contain 2 mg cynarine as the active ingredient. The placebo was described only as a “matched placebo.”

Anthropometric indices and blood pressure were measured at baseline and at the end of the study. Fasting blood samples were drawn to measure glucose; insulin; glycated hemoglobin (HbA1c); lipids; the liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase; total and direct bilirubin; and uric acid. The AST-to-platelet ratio index score (APRI) was also calculated. Liver ultrasonography was performed at baseline and at the end of the study.

Of the 100 patients who began the study, nine in the ALE group and one in the placebo group dropped out because they did not see any benefit of the treatment. No adverse effects were reported during the study. Compared with the placebo group, the ALE group experienced a significant reduction in body mass index (P=0.001) and waist circumference (P=0.009) during the study. Changes in diastolic blood pressure throughout the study did not differ between the groups (P=0.069). Systolic blood pressure increased in the ALE group and decreased in the placebo group (P=0.046). However, it should be noted that the difference between groups was a clinically insignificant absolute difference of only 3 mmHg.

Liver ultrasonographic findings revealed a significant improvement in NAFLD severity in 81.6% of patients in the ALE group and in 5.0% of patients in the placebo group (P<0.001). Compared with placebo, ALE treatment led to an increase in hepatic vein flow (P<0.001) and a reduction of portal vein diameter and liver size (P<0.001 for both). In the ALE group, ALT and AST levels were significantly lower after two months compared with those in the placebo group (P<0.001 for both). A significant reduction in total bilirubin (P=0.002) but not in direct bilirubin (P=0.802) was observed in the ALE group compared with the placebo group. Significant improvements were seen in serum uric acid levels (P<0.001), the AST/ALT ratio (P<0.01), and the APRI scores (P<0.001) after ALE treatment compared with placebo. Compared with placebo, the ALE treatment significantly reduced total cholesterol (P=0.001), LDL-C (P<0.001), non-HDL-C (P<0.001), triglycerides (P<0.001), and HDL-C (P=0.011). No significant between-group differences were seen in the changes in glucose, insulin, or HbA1c levels.

Limitations of the study include the absence of a liver biopsy, say the authors, clarifying that “although this might have added weight to our findings, clinically, the biopsy was not warranted.” As this was a pilot study, the findings should be confirmed in a larger randomized study that can be powered on the results of this study. The authors conclude that ALE supplementation had beneficial effects on liver parameters, as measured by sonography and serum markers of liver function, in patients with NAFLD.

The study was funded by Niak Pharmaceuticals and Baqiyatallah University of Medical Sciences. The authors report no conflicts of interest.

Reference

1Sahebkar A, Pirro M, Banach M, Mikhailidis DP, Atkin SL, Cicero AFG. The Lipid-lowering activity of artichoke extracts: A systematic review and metaanalysis. [published online June 13, 2017]. Crit Rev Food Sci Nutr. doi: 10.1080/10408398.2017.1332572. 

Panahi Y, Kianpour P, Mohtashami R, et al. Efficacy of artichoke leaf extract in non-alcoholic fatty liver disease: A pilot double-blind randomized controlled trial. Phytother Res. July 2018;32(7):1382-1387. doi: 10.1002/ptr.6073.

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