  Citation: Coronati, M.; Baratta, F.; Pastori, D.; Ferro, D.; Angelico, F.; Del Ben, M. Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review. Nutrients 2022, 14, 1127. https://doi.org/10.3390/ nu14061127 Academic Editor: Naoki Tanaka Received: 31 January 2022 Accepted: 4 March 2022 Published: 8 March 2022 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Review Added Fructose in Non-Alcoholic Fatty Liver Disease and in Metabolic Syndrome: A Narrative Review Mattia Coronati 1 , Francesco Baratta 1, * , Daniele Pastori 1 , Domenico Ferro 1 , Francesco Angelico 2 and Maria Del Ben 1 1 I Clinica Medica, Department of Clinical Internal, Anesthesiological and Cardiovascular Sciences, Sapienza University of Rome, 00161 Rome, Italy; coronati.1765853@studenti.uniroma1.it (M.C.); daniele.pastori@uniroma1.it (D.P.); domenico.ferro@uniroma1.it (D.F.); maria.delben@uniroma1.it (M.D.B.) 2 Department of Public Health and Infectious Diseases, Sapienza University of Rome, 00161 Rome, Italy; francesco.angelico@uniroma1.it * Correspondence: francesco.baratta@uniroma1.it Abstract: Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease and it is considered the hepatic manifestation of metabolic syndrome (MetS). Diet represents the key element in NAFLD and MetS treatment, but some nutrients could play a role in their pathophysiology. Among these, fructose added to foods via high fructose corn syrup (HFCS) and sucrose might participate in NAFLD and MetS onset and progression. Fructose induces de novo lipogenesis (DNL), endoplasmic reticulum stress and liver inflammation, promoting insulin resistance and dyslipidemia. Fructose also reduces fatty acids oxidation through the overproduction of malonyl CoA, favoring steatosis. Furthermore, recent studies suggest changes in intestinal permeability associated with fructose consumption that contribute to the risk of NAFLD and MetS. Finally, alterations in the hunger–satiety mechanism and in the synthesis of uric acid link the fructose intake to weight gain and hypertension, respectively. However, further studies are needed to better evaluate the causal relationship between fructose and metabolic diseases and to develop new therapeutic and preventive strategies against NAFLD and MetS. Keywords: NAFLD; metabolic syndrome; fructose; HFCS 1. Introduction The relationship between non-alcoholic fatty liver disease (NAFLD) and metabolic dis- orders has been widely reported. Fatty liver might be regarded as the hepatic consequence of metabolic syndrome (MetS), a disease including central obesity, hyperglycemia, high blood pressure, hypertriglyceridemia, and low HDL cholesterol levels. Therefore, a strong reciprocal association between NAFLD and MetS has been proposed [1]. The global prevalence of NAFLD and MetS are 24% [2] and 25% [3], respectively. Both conditions are strongly associated with obesity and the risk of developing cardiovascular diseases, diabetes, chronic kidney disease, and non-alcoholic steatohepatitis (NASH) related liver complications [4–8]. Treatment and prevention of NAFLD and MetS are based on lifestyle intervention. Diet represents a key point for the improvement of MetS and lifestyle correction remains the only therapeutic approach for NAFLD [9]. Guidelines recommend the association of physical activity with caloric restriction, based on the Mediterranean diet, targeting a weight loss of at least 7%, to reduce liver steatosis [10]. Free sugars play a key role in the development of obesity, type 2 diabetes mellitus (DMT2), dental caries, metabolic syndrome (MetS), cardiovascular diseases and NAFLD. The World Health Organization suggests an intake of free sugars of less than 10% of the total energy intake [11]. To ensure this, many countries have applied different strategies including the application of a “sugar tax” on high sugar food and soft drinks [12,13]. Nutrients 2022, 14, 1127. https://doi.org/10.3390/nu14061127 https://www.mdpi.com/journal/nutrients