To The Editor:

I read with interest the practice guidelines on nonalcoholic fatty liver disease (NAFLD),1 in which the authors fail to reference the association between high fructose corn syrup (HFCS) and NAFLD. The intake of HFCS, a combination of glucose and fructose, has increased over time and parallels both the obesity and NAFLD epidemics.2 Numerous studies demonstrate that the mechanism by which HFCS causes NAFLD is due to fructose. In animal models, fructose causes steatosis and fibrosis3, 4 by either increasing hepatic lipogenesis, causing activation of pyruvate dehydrogenase,5 activating inflammatory pathways,6 or up-regulating the expression of sterol regulatory element-binding protein (SREBP).7

In humans, excessive fructose intake can lead to increased hepatic lipid deposition, greater insulin resistance, and hypertriglyceridemia.8 NAFLD patients have been found to drink more HFCS soft drinks compared with healthy controls.9 A retrospective analysis of 341 NAFLD adults found that those consuming high fructose diets had more fibrosis than those consuming low fructose diets.10 A prospective controlled trial with histologic endpoints is needed to define the amount of HFCS safe for NAFLD patients and to determine the extent to which fructose contributes to the pathogenesis and progression of NAFLD. However, there are currently sufficient data to recommend that NAFLD patients refrain from excessive consumption of HFCS.


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  • 1
    Chalasani N, Younossi Z, Lavine J, Diehl AM, Brunt E, Cusi K, et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, the American Gastroenterological Association. HEPATOLOGY 2012; 55: 2005-2023.
  • 2
    Bray G, Nielsen S, Popkin M. Consumption of HFCS in beverages may play a role in the epidemic of obesity. Am J Clin Nutr 2004; 79: 537-543.
  • 3
    Anstee, Q, Goldin, R. Mouse models in NAFLD and steatohepatitis research. Int J Exp Pathol 2006; 87: 1-16
  • 4
    Davail S, Rideau N, Bernadet MD, Andre JM, Guy G, Hoo-Paris R. Effects of dietary fructose on liver steatosis in overfed mule ducks. Horm Metab Res 2005; 37: 32-35.
  • 5
    Park OJ, Cesar D, Faix D, Wu K, Shackleton CH, Hellerstein MK. Mechanisms of fructose-induced hypertriglyceridaemia in the rat. Activation of hepatic pyruvate dehydrogenase through inhibition of pyruvate dehydrogenase kinase. Biochem J 1992; 282( Pt 3): 753-757.
  • 6
    Kelley GL, Allan G, Azhar S. High dietary fructose induces a hepatic stress response resulting in cholesterol and lipid dysregulation. Endocrinology 2004; 145: 548-555.
  • 7
    Kanuri G, Spruss A, Wagnerberger S, Bischoff SC, Bergheim I. Role of TNF in the onset of fructose-induced NAFLD in mice. J Nutr Biochem 2011; 22: 527-534.
  • 8
    Lê KA, Tappy L, D'Alessio DA. Mitochondrial dysfunction and insulin resistance: a matter of lifestyle? Curr Opin Clin Nutr Metab Care 2007; 10: 494-497.
  • 9
    Abid A, Taha O, Nseir W. Soft drink consumption is associated with NAFLD independent of metabolic syndrome. J Hepatol 2009; 51: 918-924.
  • 10
    Abdelmalek MF, Suzuki A, Guy C, Unalp-Arida A, Colvin R, Johnson RV, et al. Increased fructose consumption is associated with fibrosis severity in patients with NAFLD. HEPATOLOGY 2010; 51: 1961-1971.

Melissa Palmer M.D.*, * New York University, Dix Hills, NY.