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Dietary carbohydrates and fats in nonalcoholic fatty liver disease

Abstract

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased in parallel with the epidemic of obesity. Controversy has emerged around dietary guidelines recommending low-fat–high-carbohydrate diets and the roles of dietary macronutrients in the pathogenesis of metabolic disease. In this Review, the topical questions of whether and how dietary fats and carbohydrates, including free sugars, differentially influence the accumulation of liver fat (specifically, intrahepatic triglyceride (IHTG) content) are addressed. Focusing on evidence from humans, we examine data from stable isotope studies elucidating how macronutrients regulate IHTG synthesis and disposal, alter pools of bioactive lipids and influence insulin sensitivity. In addition, we review cross-sectional studies on dietary habits of patients with NAFLD and randomized controlled trials on the effects of altering dietary macronutrients on IHTG. Perhaps surprisingly, evidence to date shows no differential effects between free sugars, with both glucose and fructose increasing IHTG in the context of excess energy. Moreover, saturated fat raises IHTG more than polyunsaturated or monounsaturated fats, with adverse effects on insulin sensitivity, which are probably mediated in part by increased ceramide synthesis. Taken together, the data support the use of diets that have a reduced content of free sugars, refined carbohydrates and saturated fat in the treatment of NAFLD.

Key points

  • Nonalcoholic fatty liver disease (NAFLD), total energy intake and intake of free sugars and refined carbohydrates have increased in parallel; de novo lipogenesis, which produces saturated fat from sugars, contributes to NAFLD.

  • Saturated fat intakes have remained well above the recommended maximum of 10% total energy in many developed countries/regions worldwide, which is of concern in NAFLD as well as cardiovascular disease.

  • The American Association for the Study of Liver Diseases, in contrast to the European Association for the Study of the Liver, did not make any recommendation regarding macronutrient intake in NAFLD and instead called for rigorous, prospective, longer-term trials with histopathological end points.

  • Analysis of existing trials shows that high-fat–low-carbohydrate diets containing high saturated fat increase intrahepatic triglyceride (IHTG) content more than low-fat–high-carbohydrate diets.

  • Saturated fat-enriched diets increase IHTG more than polyunsaturated or monounsaturated diets; ceramides probably contribute to saturated fat-induced adverse metabolic and cardiovascular consequences.

  • The limited data available support the use of a Mediterranean diet that is low in saturated fat with high amounts of monounsaturated fat and dietary fibre in the treatment of NAFLD.

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Fig. 1: Metabolic fates of free sugars and SFAs.
Fig. 2: Effects of fats and carbohydrates on liver fat content.
Fig. 3: Metabolic effects of excessive intakes of saturated fat and free sugars.
Fig. 4: Sugar metabolism and regulation.

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Acknowledgements

L.H. is a British Heart Foundation Senior Research Fellow (FS/15/56/31645). P.K.L. is supported by grants from the Sigrid Jusélius, Instrumentarium Science and Novo Nordisk Foundations.

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Yki-Järvinen, H., Luukkonen, P.K., Hodson, L. et al. Dietary carbohydrates and fats in nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol 18, 770–786 (2021). https://doi.org/10.1038/s41575-021-00472-y

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