A CONSORT-compliant, randomized, double-blind, placebo-controlled pilot trial of purified anthocyanin in patients with nonalcoholic fatty liver disease

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease that can progress to cirrhosis and liver failure. Anthocyanin, a member of the flavonoid family, has been shown to ameliorate NAFLD-associated pathologies in rodents.The aim of this CONSORT-compliant pilot study is to evaluate the effects of anthocyanin supplementation on insulin resistance and liver injury biomarkers in patients with NAFLD.A total of 74 subjects with NAFLD were divided into 2 groups in this double-blind, randomized study. Patients received either purified anthocyanin (320 mg/d) derived from bilberry and black currant or placebo for 12 weeks. Diet, physical activity, anthropometric parameters, glucose tolerance, and a set of biomarkers related to NAFLD were evaluated before and after intervention.No significant differences were observed in nutrient intake, physical activity, anthropometric parameters, or plasma lipid profile between patients receiving anthocyanin or placebo. Compared to controls, the anthocyanin group exhibited significant decreases (P < 0.05, all comparisons) in plasma alanine aminotransferase (-19.1% vs 3.1%), cytokeratin-18 M30 fragment (-8.8% vs 5.6%) and myeloperoxidase (-75.0% vs -44.8%). Significant decreases from baseline in fasting blood glucose and homeostasis model assessment for insulin resistance were observed in the anthocyanin group; however, these differences were not significant relative to placebo controls. In addition, the oral glucose tolerance test indicated that anthocyanin supplementation significantly decreased the 2-hour loading glucose level compared to control (-18.7% vs -3.8%, P = 0.02).A 12-week supplement of purified anthocyanin improved insulin resistance, indicators of liver injury, and clinical evolution in NAFLD patients. Further studies are warranted to determine the clinical applications of anthocyanin in NAFLD.This trial was registered at clinicaltrials.gov as NCT01940263.

FIGURE 1

Consolidated standards of reporting trials flow diagram of the study participants.

FIGURE 2

Effect of the 12-week anthocyanin intervention on ALT levels in NAFLD patients. The columns and error bars indicate medians with quartiles. After intervention, no differences were observed between the 2 groups across intragender comparisons; however, the total mean reduction of ALT levels in the anthocyanin group was greater than that in the placebo group (a), P compared difference between 2 groups by Mann–Whitney U test. Compared with baseline, there is a remarkable decline in ALT after a 12-week intervention in males, females, and total patients in the anthocyanin group (b, c), but only in females in the placebo group (b, d). P compared with the basal values in each group by Wilcoxon matched pairs signed rank test.

FIGURE 3

Changes in glucose concentration measured 2 h after a 75-g oral glucose load in the 2 treatments during the study period. P compared difference between 2 groups by independent-sample t test.

FIGURE 4

Correlation between changes in plasma ALT activities and the levels of CK-18 M30; n = 37 in each group. The data were evaluated by using Pearson correlation coefficients (r).