Archives of Toxicology

, Volume 91, Issue 4, pp 1545–1563 | Cite as

Dietary fructose as a risk factor for non-alcoholic fatty liver disease (NAFLD)

  • Salamah Mohammad AlwahshEmail author
  • Rolf GebhardtEmail author
Review Article


Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic syndrome affecting about one-third of the population worldwide and has progressive pathological potential for liver cirrhosis and cancer through non-alcoholic steatohepatitis (NASH). Here we have reviewed the possible contribution of fructose to the pathophysiology of NAFLD. We critically summarize the current findings about several regulators, and their potential mechanisms, that have been studied in humans and animal models in response to fructose exposure. A novel hypothesis on fructose-dependent perturbation of liver regeneration and metabolism is advanced. Fructose intake could affect inflammatory and metabolic processes, liver function, gut microbiota, and portal endotoxin influx. The role of the brain in controlling fructose ingestion and the subsequent development of NAFLD is highlighted. Although the importance for fructose (over)consumption for NAFLD in humans is still debated and comprehensive intervention studies are invited, understanding of how fructose intake can favor these pathological processes is crucial for the development of appropriate noninvasive diagnostic and therapeutic approaches to detect and treat these metabolic effects. Still, lifestyle modification, to lessen the consumption of fructose-containing products, and physical exercise are major measures against NAFLD. Finally, promising drugs against fructose-induced insulin resistance and hepatic dysfunction that are emerging from studies in rodents are reviewed, but need further validation in human patients.


Insulin resistance Inflammation Metabolic syndrome (MetS) Gut microbiota Herbal medicine Biomarkers The brain Ethanol Humans Oxidative stress Liver regeneration ATP 



Cytochrome 450 2E1


Endoplasmic reticulum


Glucose transporter


High-density lipoprotein


High-fructose corn syrup


High-fat diet


Insulin resistance


Insulin receptor substrate 1/2


Lipocalin 2


High-density lipoprotein






Melanocortin receptor 4


Metabolic syndrome


Non-alcoholic fatty liver disease


Non-alcoholic steatohepatitis


Plasminogen activator inhibitor-1


Reactive oxygen species


Type 2 diabetes mellitus




Toll-like receptor 4


Tumor necrosis factor-α



S.M.A. and R.G. conceived, designed, wrote, and approved the final manuscript. The authors thank Dr. John Hallett, MCR Centre for Regenerative Medicine, The University of Edinburgh, UK, for proofreading the paper.


This study was supported by grants from the Bundesministerium für Forschung und Technologie (BMBF) in the framework of the Systems Biology initiative “Virtual Liver Network” to RG (Grant: 0315735).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Faculty of Medicine, Institute of BiochemistryUniversity of LeipzigLeipzigGermany
  2. 2.MCR Centre for Regenerative MedicineUniversity of EdinburghEH16 4UU EdinburghUK

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