Dietary carbohydrates and fats in nonalcoholic fatty liver disease

Yki-Järvinen, Hannele; Luukkonen, Panu K.; Hodson, Leanne; Moore, J. Bernadette

doi:10.1038/s41575-021-00472-y

Cited by 294Liver Disease Diagnosis and TreatmentDiet, Metabolism, and DiseaseAlcohol Consumption and Health Effects

Dietary carbohydrates and fats in nonalcoholic fatty liver disease

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Yki-Järvinen, Hannele, Luukkonen, Panu K., Hodson, Leanne, Moore, J. Bernadette·2021·Nature Reviews Gastroenterology & Hepatology

DOI 10.1038/s41575-021-00472-y

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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.

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Hypocaloric low-carbohydrate diets and low-fat diets appear to be similarly effective in reducing liver lipid content and related biomarkers in individuals with MASLD.
“Hypocaloric low-carbohydrate diets and low-fat diets appear to be similarly effective in reducing liver lipid content and related biomarkers. 289,290”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [289]
Saturated fat has been shown to have a negative effect on liver steatosis in several short-term clinical trials.
“Saturated fat has been shown to have a negative effect on liver steatosis in several short-term clinical trials. 289”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [289]
Intake of added sugars, especially fructose, plays a major role in MASLD development.
“Intake of added sugars, especially fructose, plays a major role in MASLD development. 289”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [289]

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Authors: Yki-Järvinen, H., Luukkonen, P. K., Hodson, L., & Moore, J. B.
Affiliations: University of Helsinki (FI)
University of Oxford (GB)
University of Leeds (GB)
ORCID: Luukkonen, Panu K.
Hodson, Leanne
Moore, J. Bernadette
Venue: Nature Reviews Gastroenterology & Hepatology
Publisher: Springer Science and Business Media LLC
Published: 2021-07-13
Volume: 18
Issue: 11
Pages: 770-786
ISSN: 1759-5045 (ISSN-L)
1759-5053
DOI: 10.1038/s41575-021-00472-y
OpenAlex: W3178703016
Cited by: 294
References: 221
Citations by year: 2026: 51 · 2025: 81 · 2024: 67 · 2023: 41 · 2022: 46 · 2021: 8
FWCI: 6.18
Type: journal article
Language: en
Open access: green
ora.ox.ac.uk
Licence: cc-by
www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Gastroenterology & Hepatology (publishedVersion)
PubMed (publishedVersion)
White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
Oxford University Research Archive (ORA) (University of Oxford) (submittedVersion, cc-by)
Työväentutkimus Vuosikirja (submittedVersion)
Funders: British Heart Foundation (FS/15/56/31645)
Novo Nordisk
Novo Nordisk Fonden (NNF18OC0054504, NNF19OC0057503)
Biotechnology and Biological Sciences Research Council (BBS/E/F/000PR10347, BB/N005600/1, BBS/E/F/00044434)
Topics: Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords: non-alcoholic fatty liver disease, dietary carbohydrates, dietary fat, free sugars, fructose, glucose, saturated fat, polyunsaturated fat, monounsaturated fatty acids, intrahepatic triglyceride, hepatic lipid accumulation, insulin sensitivity, ceramide synthesis, bioactive lipids, macronutrient metabolism, obesity, low-fat high-carbohydrate diet
MeSH terms: Dietary Sugars, Ceramides, Dietary Carbohydrates, Dietary Fats, Dietary Fats, Unsaturated, Fructose, Glucose, Humans, Insulin Resistance, Liver, Triglycerides, Non-alcoholic Fatty Liver Disease

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Dietary carbohydrates and fats in nonalcoholic fatty liver disease

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