Abstract

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent liver disease in industrialized countries. It is regarded as the hepatic manifestation of the metabolic syndrome (MetS) resulting from insulin resistance. Moreover, insulin resistance impairs glycogen synthesis, postprandially diverting a substantial amount of carbohydrates to the liver and storing them there as fat. NAFLD has far-reaching metabolic consequences involving glucose and lipoprotein metabolism disorders and risk of cardiovascular disease, the leading cause of death worldwide. No pharmaceutical options are currently approved for the treatment of NAFLD. Exercise training and dietary interventions remain the cornerstone of NAFLD treatment. Current international guidelines state that the primary goal of nutritional therapy is to reduce energy intake to achieve a 7%–10% reduction in body weight. Meal replacement therapy (formula diets) results in more pronounced weight loss compared to conventional calorie-restricted diets. However, studies have shown that body mass index (BMI) or weight reduction is not obligatory for decreasing hepatic fat content or to restore normal liver function. Recent studies have achieved significant reductions in liver fat with eucaloric diets and without weight loss through macronutrient modifications. Based on this evidence, an integrative nutritional therapeutic concept was formulated that combines the most effective nutrition approaches termed “liver-fasting.” It involves the temporary use of a low calorie diet (total meal replacement with a specific high-protein, high-soluble fiber, lower-carbohydrate formula), followed by stepwise food reintroduction that implements a Mediterranean style low-carb diet as basic nutrition.

Highlights

  • A non-alcoholic fatty liver is defined as one with hepatic steatosis in the absence of significant alcohol consumption or other causes of secondary steatosis [1]

  • The second largest contribution to liver fat in Non-alcoholic fatty liver disease (NAFLD) patients comes from carbohydrate input via de novo lipogenesis (DNL) with (26%), and the third largest proportion comes from dietary fat (15%)

  • There have been ample studies suggesting that supplementing long-chain omega-3 fatty acids (EPA and docosahexaenoic acid (DHA)) in the range of 2–5 g per day independently contributes to reductions in liver fat content, a finding that was confirmed by a recent meta-analysis of randomized controlled trials [66]

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Summary

Introduction

A non-alcoholic fatty liver is defined as one with hepatic steatosis in the absence of significant alcohol consumption or other causes of secondary steatosis [1]. The most commonly used acronym is NAFLD (non-alcoholic fatty liver disease). NAFLD encompasses the entire spectrum of liver diseases characterized by increased fat storage in the liver from steatosis without inflammation (non-alcoholic fatty liver; NAFL) to non-alcoholic steatohepatitis (NASH), cirrhosis, liver failure, and/or hepatocellular carcinoma [1,2]. In patients with T2DM, the co-existence of NAFLD doubles cardiovascular disease risk [10]. In Western countries, the prevalence of NAFLD ranges from 30% to 40% in the general population [1], whilst risk increases to greater than twofold in patients with T2DM, where it is reported in 60%–70% of these patients [11]. Given the rising obesity-related health problems and trends toward an aging population, the prevalence of NAFLD is projected to increase nationally and globally [3].

Nutritional Aspects of Pathogenesis
Hyperinsulinemia Triggers “De Novo Lipogenesis” from Carbohydrates
Dietary Fats Are Involved
Nutritional Therapy
Hypocaloric Diets
Low-Carbohydrate Dietary Patterns
Meal Replacement Therapy
Eucaloric Diets
The Role of Dietary Fat
The Role of Dietary Protein
The Role of Dietary Carbohydrate
Protective Dietary Compounds
Findings
Conclusions
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