GENISTEIN SUPPLEMENTATION IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A RANDOMIZED, CONTROLLED TRIAL

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. NAFLD development is associated with adiposity and insulin resistance, which amplifies liver fat accumulation, the first hit in the two-hit hypothesis. The second hit is oxidative stress and inflammation that can cause NASH and fibrosis (1). Many nutritive and non-nutritive compound including vitamin E, pioglitazone and metformin have been proposed to impact these two hits but none of them had a consistent effect. The beneficial effect of genistein has indicated on metabolic disorders and inflammatory state(2, 3). The aim of this study was to investigate the effect of genistein supplementation on nonalcoholic fatty liver disease (NAFLD) as the hepatic manifestation of metabolic syndrome.Methods: In the present randomized double-blind controlled trial, a total of 82 patients that acquired inclusion criteria were recruited. These criteria were aging 18-69 years old, diagnosing with steatosis of grade ≥2 by ultrasound imaging, not having viral hepatitis, cirrhosis or other chronic systemic diseases, not being pregnant or alcohol consumers, not using antidiabetic, lipid-lowering drugs or vitamin supplements. Participants were daily supplemented with either 250 mg genistein (n = 41) or placebo (n = 41) for 8-weeks. Both groups were instructed to follow an energy-balanced diet and physical activity recommendations. Anthropometric measures including height, weight, waist and hip circumference and body composition were assessed. In addition, biochemical parameters covering glycemic, lipidemic, enzymatic, oxidative and inflammatory indices were measured before and after the intervention.At the end of the study, the genistein group had a lower level of serum insulin (p = 0.001) and homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.041) compare to the placebo group. In addition serum malondialdehyde (MDA) (p = 0.004), tumor necrosis factor-a (TNF-a) (p = 0.045) and interleukin (IL-6) (p = 0.018) also were lower in the genistein group. Compare with placebo, genistein supplementation significantly reduced waist to hip ratio (p = 0.021), body fat percentage (p = 0.015) and triglyceride (p = 0.018). However, there were no significant changes in BMI, fasting blood glucose (p = 0.122), alanine aminotransferase (ALT) (p = 0.536) or aspartate aminotransferase (AST) (p = 0.265) between the two groups.Conclusion: It s been suggested that severity of insulin resistance is in correlation with NAFLD progression and development of fibrosis (4). Our result showed that oral supplementation with 250 mg genistein for 8-weeks can reduce insulin resistance. This was along with results of other studies that reported isoflavones and especially genistein may be an antidiabetic agent (5, 6). The genistein facilitates glucose uptake by the promotion of Glucose transporter type 4 translocation to the cell membrane. The beneficial effect of genistein extends to anti-oxidative and anti-inflammatory activity in patients with NAFLD. These properties were reported previously in human studies and mostly were liked to 1- reactive oxygen species scavenging action of genistein molecule, 2- increase in anti-oxidant enzymes gene expression (7-10). Reviewing recent studies propose that genistein supplementation could be effective in modifying lipid profile, however, improvement only in serum triglyceride in our study is an indication of the need for studies with longer intervention and larger sample size to reveal other beneficial effects of genistein.

کلیدواژه ها:

Non-alcoholic fatty liver disease ، Genistein ، Insulin resistance ، Inflammation