Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes§


  • Potential conflict of interest: R.J.J. published a lay book (“The Sugar Fix”) that discusses the potential role of fructose in obesity and fatty liver and has a patent application on lowering uric acid to reduce fatty liver disease.

  • The study was supported by the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disorders (NIH/NIDDK; grant nos.: RO1-DK060427 and UO1-DK57149) and the John Hopkins University School of Medicine General Clinical Research Center (M01-RR00052). R.J.J. is supported by grant HL-68607. M.F.A. is supported by a NIH/NIDDK K23 Career Development Award (K23-DK062116).

  • §

    This study was presented at the American Association for the Study of Liver Diseases 60th Annual Meeting, Boston, MA, October 30-November 3, 2009.


Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hepatic ATP depletion and impaired ATP recovery. The degree of ATP depletion after an intravenous (IV) fructose challenge test in low- versus high-fructose consumers was assessed. We evaluated diabetic adults enrolled in the Action for Health in Diabetes Fatty Liver Ancillary Study (n = 244) for whom dietary fructose consumption estimated by a 130-item food frequency questionnaire and hepatic ATP measured by phosphorus magnetic resonance spectroscopy and uric acid (UA) levels were performed (n = 105). In a subset of participants (n = 25), an IV fructose challenge was utilized to assess change in hepatic ATP content. The relationships between dietary fructose, UA, and hepatic ATP depletion at baseline and after IV fructose challenge were evaluated in low- (<15 g/day) versus high-fructose (≥15 g/day) consumers. High dietary fructose consumers had slightly lower baseline hepatic ATP levels and a greater absolute change in hepatic α-ATP/ inorganic phosphate (Pi) ratio (0.08 versus 0.03; P = 0.05) and γ-ATP /Pi ratio after an IV fructose challenge (0.03 versus 0.06; P = 0.06). Patients with high UA (≥5.5 mg/dL) showed a lower minimum liver ATP/Pi ratio postfructose challenge (4.5 versus 7.0; P = 0.04). Conclusions: High-fructose consumption depletes hepatic ATP and impairs recovery from ATP depletion after an IV fructose challenge. Subjects with high UA show a greater nadir in hepatic ATP in response to fructose. Both high dietary fructose intake and elevated UA level may predict more severe hepatic ATP depletion in response to fructose and hence may be risk factors for the development and progression of NAFLD. (HEPATOLOGY 2012;56:952–960)