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

Journal Of Hepatology

May 2018 Volume 68, Issue 5, Pages 1063–1075

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

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TAKE-HOME MESSAGE

While we have known for many years that fructose and beverages sweetened with high fructose corn syrup can contribute to nonalcoholic fatty liver disease, this is an excellent review of the literature to date on this topic. In addition, it postulates the potential mechanisms that could be contributing to fructose's contribution to the development of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. It also highlights the factors that can potentiate the effect that fructose has on the liver, including genetic mechanisms, the role of fructokinase, high-fat diets, and alcohol.

While certainly more research is needed, this review is beneficial when speaking to our patients and providing guidance on dietary changes that may improve their disease.

– Natasha VonRoenn, MD

Summary

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.

Continue to article: https://www.journal-of-hepatology.eu/article/S0168-8278(18)30066-7/fulltext