Applied nutritional investigationGood adherence to the Mediterranean diet reduces the risk for NASH and diabetes in pediatric patients with obesity: The results of an Italian Study
Introduction
During the last decade, nonalcoholic fatty liver disease (NAFLD) became the most common cause of chronic hepatopathies in children and adolescents [1]. Actually, 4 to 11% of the general pediatric population in industrialized countries is affected by NAFLD, reaching a rate of 70% among overweight and obese children [2].
NAFLD represents a cluster of liver damage, characterized by fat accumulation in the hepatocytes (exceeding 5% of liver cells), in the absence of excessive alcohol intake or other causes of hepatic steatosis [3]. Hepatic manifestations of NAFLD range from simple fat accumulation in the hepatocytes (simple steatosis) to advanced forms of liver involvement, with inflammation and fibrosis (nonalcoholic steatohepatitis [NASH]), up to cirrhosis and hepatocellular carcinoma, which leads to liver-related death [4].
NAFLD is considered a “multihit disease” in which genetic, epigenetic, and environmental factors interact in the development of liver damage and metabolic disarray. In the recent past, important advances in the knowledge of NAFLD pathogenesis have been made and the multihits theory is now commonly adopted [5]. The accumulation of insulin resistance (IR) and triacylglycerols (TGs) in the hepatocytes cause hepatic steatosis, making the liver more susceptible to secondary hits, such as oxidative stress, mitochondrial dysfunction, immune system response and inflammation, and gut-derived bacterial endotoxinemia. These noxa induce the progression of liver damage with development of necroinflammation and fibrosis, in selected patients with genetic susceptibilities [6].
Several data have demonstrated that diets high in saturated fats and refined sugars, mainly fructose, contribute to metabolic disarray leading to NAFLD and metabolic syndrome (MetS) [7]. As of now, there are no pharmacologic treatments for NAFLD; therefore, weight loss represents the cornerstone of treatment [8]. Currently, there are no clear evidence-based guidelines establishing the optimal dietary interventions for children with NAFLD. Available evidence suggests that a reduction in sugar and an increase in polyunsaturated fatty acids may not only induce a reduction in IR and lipogenesis, but also have an antiinflammatory/antifibrogenetic effect [9]. In the last 10 y, the Mediterranean diet (MD) has been shown to represent an ideal diet for all age groups. The MD plays an important role in the prevention of cardiovascular and cerebrovascular diseases, diabetes, obesity, neurodegenerative illnesses, cancer, and NAFLD [10].
The MD is characterized by the intake of a large quantity of vegetables, fruits, bread and other forms of cereals, rice, legumes, and nuts. Moreover, it includes extra virgin olive oil as the main fat source, moderate amounts of dairy products, significant amounts of fish, and red meat in small quantities. Therefore, the MD is characterized by a low content of saturated fatty acids and a high monounsaturated fatty acids, as well as high amounts of fiber and carbohydrates, and important amounts of antioxidants [11], [12]. Based on its lipid profile, with a good balanced ratio ω-3 to ω-6 polyunsaturated fatty acids, insulin-sensitizing effect, and antioxidant capacity, the MD has a beneficial role in the management of obesity/overweight-related NAFLD. In 2004, Serra-Majem developed a clinical index based on a nutritional score that evaluates the adherence to MD and the quality of diet in children and adolescents (Mediterranean Diet Quality Index for children and adolescents [KIDMED]) [13]. Several data are available regarding the well-known association between poor adherence to the MD and overweight/obesity both in adults and children [14], [15]. Furthermore, a significant association between the MD and NAFLD has been reported in adults, demonstrating an association between poor adherence to MD and severity of liver damage and IR [16]. Ryan reported the positive therapeutic effect of the MD on NAFLD in a small group of adults with NAFLD, in which 6-wk of treatment with the MD induced an amelioration of liver steatosis and insulin sensitivity, even without weight loss [17]. Limited data are available about the MD and NAFLD in children. Recently, Cakir et al. reported that low adherence to the MD (low KIDMED score), in association with high body mass index (BMI), was a predictor of NAFLD in children [18]. In this study, the diagnosis of NAFLD was not made on liver biopsy, and therefore, a correlation between the MD and histologic damage was not available.
The aim of the present study was to analyze the association between the adherence to the MD and NAFLD, with laboratory and histologic evaluation, in a group of children and adolescents with obesity/overweight.
Section snippets
Study population
The present study enrolled white children (ages 10–17 y) with obesity who were referred to Hepatometabolic Unit of Children's Hospital from March 2014 to November 2015.
Study protocol
Abdominal ultrasound was performed in all patients by the same radiologist using an Acuson Sequoia C512 scanner equipped with a 15 L8 transducer (Universal Diagnostic Solutions, Oceanside, CA, USA). Liver steatosis was defined according to criteria based on the presence of abnormally intense, high-level echoes arising from the
Results
In the present study, we evaluated 243 patients. All were obese/overweight (BMI 28.16 ± 6.34 kg/m2). Based on the abdominal ultrasound finding of hepatic steatosis, the patients were divided in two groups: those without fatty liver (FL−; 77 patients, 31.7%) and those with fatty liver (FL+; 166 patients, 68.3%). In the FL+ group, 75 patients (45.2%) had severe steatosis, 45 (27.1 %) moderate, and 46 (27.7%) mild steatosis. Among patients with echographic evidence of fatty liver, 100 underwent to
Discussion
The MD has been largely evaluated in both adults and children for its beneficial effects in terms of prevention of obesity, MetS, and cardiovascular diseases [27]. It has been reported to be a prudent dietary pattern for noncommunicable disease prevention and has been promoted as a model of healthy eating [28].
Several previous data have proved an association between poor adherence to the MD and IR and obesity. Considering the recent findings demonstrating a relationship between diet composition
Conclusions
Based on the results from the present study and the previously available data on adults and children, the MD should represent a useful and appropriate therapeutic option in the area of behavioral changes. Guidelines for the treatment of pediatric NAFLD/NASH are lacking and none of the tested drugs has shown a completely satisfactory profile, with efficacy on histologic damage, mainly fibrosis. Well-designed dietary intervention trials are needed to define the real efficacy of the MD in
Acknowledgments
The authors acknowledge Franco Angelico and his suggestions in setting up the manuscript.
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