No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men

Gastroenterology. 2013 Nov;145(5):1016-1025.e2. doi: 10.1053/j.gastro.2013.07.012. Epub 2013 Jul 19.


Background & aims: Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease. We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol (TAG) concentration and other liver parameters.

Design: In a double-blind study, we randomly assigned 32 healthy but centrally overweight men to groups that received either a high-fructose or high-glucose diet (25% energy). These diets were provided during an initial isocaloric period of 2 weeks, followed by a 6-week washout period, and then again during a hypercaloric 2-week period. The primary outcome measure was hepatic level of TAG, with additional assessments of TAG levels in serum and soleus muscle, hepatic levels of adenosine triphosphate, and systemic and hepatic insulin resistance.

Results: During the isocaloric period of the study, both groups had stable body weights and concentrations of TAG in liver, serum, and soleus muscle. The high-fructose diet produced an increase of 22 ± 52 μmol/L in the serum level of uric acid, whereas the high-glucose diet led to a reduction of 23 ± 25 μmol/L (P < .01). The high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance, whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 (P = .03). During the hypercaloric period, participants in the high-fructose and high-glucose groups had similar increases in weight (1.0 ± 1.4 vs 0.6 ± 1.0 kg; P = .29) and absolute concentration of TAG in liver (1.70% ± 2.6% vs 2.05% ± 2.9%; P = .73) and serum (0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L; P = .91), and similar results in biochemical assays of liver function. Body weight changes were associated with changes in liver biochemistry and concentration of TAGs.

Conclusions: In the isocaloric period, overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes. However, in the hypercaloric period, both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups. This indicates an energy-mediated, rather than a specific macronutrient-mediated, effect. Clinical no: NCT01050140.

Keywords: ATP; BMI; C-reactive protein; CRP; EGP; HFCS; HOMA-IR; HTGC; IL; Insulin Resistance; MR; MRS; NAFLD; NEFA; Obesity; Pi; Steatosis; TAG; TE; TNF; TR; adenosine triphosphate; body mass index; echo time; endogenous glucose production; hepatic triglyceride content; high-fructose corn syrup; homeostasis model assessment of insulin resistance; inorganic phosphate; interleukin; magnetic resonance; magnetic resonance spectroscopy; nonalcoholic fatty liver disease; nonesterified fatty acid; repetition time; triacylglycerol; tumor necrosis factor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adolescent
  • Adult
  • Dietary Carbohydrates / pharmacology*
  • Double-Blind Method
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Fructose / pharmacology*
  • Glucose / pharmacology*
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Humans
  • Insulin Resistance / physiology
  • Liver / drug effects*
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Outcome Assessment, Health Care
  • Overweight / metabolism*
  • Triglycerides / metabolism*
  • Uric Acid / metabolism
  • Young Adult


  • Dietary Carbohydrates
  • Triglycerides
  • Uric Acid
  • Fructose
  • Adenosine Triphosphate
  • Glucose

Associated data