The Effect of Zinc Supplementation on Steatosis Severity and Liver Function Enzymes in Overweight/Obese Patients with Mild to Moderate Non-alcoholic Fatty Liver Following Calorie-Restricted Diet: a Double-Blind, Randomized Placebo-Controlled Trial Mojdeh Fathi 1 & Pezhman Alavinejad 2 & Zahra Haidari 3 & Reza Amani 1 Received: 3 November 2019 /Accepted: 13 December 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract The role of zinc is known in balancing the oxidant/antioxidant system and also in improving insulin resistance in many diseases. Recently, in vivo and in vitro studies revealed roles of zinc on lipophagy and suppressing hepatic lipid deposition. The present study is the first double-blind randomized clinical trial that investigated the effect of zinc supplement on clinical manifestations and anthropometric parameters of overweight/obese non-alcoholic fatty liver patients following calorie-restricted diet. Fifty-six overweight/obese subjects with confirmed non-alcoholic fatty liver disease (NAFLD) using ultrasonography were randomized to treatment (calorie-restricted diet plus 30 mg/day zinc supplement) or placebo (calorie-restricted diet and placebo) groups. Serum liver enzymes and liver steatosis were measured at the baseline and 12 weeks post-intervention. Anthropometric measurements and food recalls were collected at the beginning, weeks 6 and 12. Zinc supplementation significantly elevated serum zinc concentrations in the treatment group (p < 0.001). Treatment also reduced alanine aminotransferase and γ-glutamyl transpeptidase enzymes in the treatment group (p < 0.05). Waist circumference was also significantly lowered in the zinc group (p < 0.05). Liver steatosis and fatty liver index changes were not significant between the groups. Overall, beneficial effects of zinc supplementation were shown on serum levels of zinc and liver enzymes in overweight/obese NAFLD patients. Keywords Zinc supplement . Dietary weight loss . Non-alcoholic fatty liver . Steatosis . Liver enzymes . Anthropometric Introduction Non-alcoholic fatty liver disease (NAFLD), as the most com- mon type of liver disorder, is approximately prevalent in 20– 40% of the general population, whereas it is estimated to be present in up to 80% of obese individuals [1]. Given the prev- alence of overweight/obesity is continuing to rise with regard to its positive association with NAFLD as an independent risk factor of cardiovascular disease (CVD), worldwide concern about NAFLD has increased [2, 3]. Large cohort studies showed higher BMI was significantly related to NAFLD fibrosis regardless of metabolic syndrome [4, 5]. Despite the fact that dietary fat intake and hepatic de novo lipogenesis are involved in hepatic triglyceride accumulation, free fatty acids, the main product of visceral adipose tissue lipolysis, are the main source of liver triglycerides in NAFLD [6]. Furthermore, evidence showed that overexpression of FTO gen, the obesity-associated gene, increases oxidative stress and lipogenesis in the animal model of NAFLD [7]. Obesity induces metabolic abnormality lead- ing to apoptosis and more severe liver pathologies via lyso- somal and mitochondrial as well as endoplasmic reticulum dysfunction. Generally, studies demonstrated oxidative stress as a key factor that accelerates steatosis and also stimuli to steatohepatitis and fibrosis [8–10]. Indeed, liver steatosis in- duces hepatic insulin resistance that leads to metabolic dys- regulation such as hyperglycemia, hypertriglyceridemia, and * Reza Amani r_amani@mail.mui.ac.ir 1 Department of Clinical Nutrition, School of Nutrition and Food Science, Food Security Research Center, Isfahan University of Medical Sciences, Isfahan, Isfahan Province, Iran 2 Alimentary Tract Research Center, Ahvaz Imam Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Khuzestan Province, Iran 3 Department of Biostatistics and Epidemiology, School of Health, Isfahan University of Medical Sciences, Isfahan, Isfahan Province, Iran Biological Trace Element Research https://doi.org/10.1007/s12011-019-02015-8