Fructose and sugar: A major mediator of non-alcoholic fatty liver disease

Thomas Jensen, Manal F. Abdelmalek, Shelby Sullivan, Kristen J. Nadeau, Melanie Green, Carlos Roncal, Takahiko Nakagawa, Masanari Kuwabara, Yuka Sato, Duk Hee Kang, Dean R. Tolan, Laura G. Sanchez-Lozada, Hugo R. Rosen, Miguel A. Lanaspa, Anna Mae Diehl, Richard J. Johnson

Research output: Contribution to journalReview articlepeer-review

563 Scopus citations

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence suggests that diets high in sugar (from sucrose and/or high-fructose corn syrup [HFCS]) not only increase the risk of NAFLD, but also non-alcoholic steatohepatitis (NASH). Herein, we review the experimental and clinical evidence that fructose precipitates fat accumulation in the liver, due to both increased lipogenesis and impaired fat oxidation. Recent evidence suggests that the predisposition to fatty liver is linked to the metabolism of fructose by fructokinase C, which results in ATP consumption, nucleotide turnover and uric acid generation that mediate fat accumulation. Alterations to gut permeability, the microbiome, and associated endotoxemia contribute to the risk of NAFLD and NASH. Early clinical studies suggest that reducing sugary beverages and total fructose intake, especially from added sugars, may have a significant benefit on reducing hepatic fat accumulation. We suggest larger, more definitive trials to determine if lowering sugar/HFCS intake, and/or blocking uric acid generation, may help reduce NAFLD and its downstream complications of cirrhosis and chronic liver disease.

Original languageEnglish
Pages (from-to)1063-1075
Number of pages13
JournalJournal of Hepatology
Volume68
Issue number5
DOIs
StatePublished - May 2018

Bibliographical note

Publisher Copyright:
© 2018 European Association for the Study of the Liver

Keywords

  • Hepatic inflammation
  • Hepatic steatosis
  • Insulin resistance
  • Sugar consumption
  • Uric acid

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