Beyond Body Weight-Loss: Dietary Strategies Targeting Intrahepatic Fat in NAFLD

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.