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Genistein Improves Metabolic Parameters in Non-Alcoholic Fatty Liver Disease

11/21/2018 12:09:17 PM
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and occurs on a continuum from simple steatosis to steatohepatitis (NASH) and cirrhosis. The pathophysiology of NAFLD is thought to begin with insulin resistance and progress because of oxidative stress and inflammation. In the absence of pharmaceutical treatments for NAFLD, the mainstay approach to therapy is dietary modification, exercise, and weight loss. In addition, antioxidant supplementation has been explored as a therapeutic option in NAFLD. 
Genistein is a soy isoflavone that has demonstrated antioxidant, anti-inflammatory, and insulin regulating effects in animal studies and experimental models of NAFLD. A double-blind, randomized, placebo-controlled trial, published in Clinical Nutrition in 2018, evaluated the effects of genistein supplementation on metabolic parameters in patients with NAFLD.
A total of 82 adults with NAFLD (defined as steatosis ≥ 2 by ultrasound) were randomized to genistein capsules (250 mg/day, manufactured by BOS SCI, USA) or a placebo for 8 weeks. Both groups were given similar dietary and physical activity recommendations. The primary outcome measure was change in homeostasis model assessment for insulin resistance (HOMA-IR), with secondary outcomes that included changes in fasting blood sugar, fasting insulin, lipid profiles aminotransferases, proinflammatory cytokines, malondialdehyde (MDA), and anthropometric measures.
Results showed significant improvement in the genistein group in the primary outcome of change in HOMA-IR, with a mean reduction from 28.96 at baseline to 26.29 at week 8 (p=.007). The change in HOMA-IR was also statistically significant when compared with placebo (p=.04). Significant improvements were also observed in the genistein group for the secondary endpoints of fasting insulin (from 112.36 mg/dL at baseline to 102.58 at week 8), serum MDA, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and serum triglycerides. There were no significant changes in fasting glucose or aminotransferases (ALT and AST). 
For anthropometric measures, the genistein group experienced significant reductions in weight, body mass index, waist circumference, and body fat percentage along with increases in skeletal muscle mass and fat-free mass from baseline to week 8. However, only waist circumference and body fat percentage were significantly different than the placebo group.
The main findings from this study were that genistein supplementation improved biomarkers of insulin resistance, inflammation, and oxidative stress in patients with NAFLD. Given that these mechanisms underlie the progression of NAFLD to NASH and cirrhosis, genistein might be a promising option, in conjunction with lifestyle change, to slow the progression of NAFLD.
Amanat S, Eftekhari MH, Fararouei M, Bagheri Lankarani K, Massoumi SJ. Genistein supplementation improves insulin resistance and inflammatory state in non-alcoholic fatty liver patients: A randomized, controlled trial. Clin Nutr. 2018; 37: 1210-1215.

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