A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans

Am J Clin Nutr. 2006 Dec;84(6):1374-9. doi: 10.1093/ajcn/84.6.1374.


Background: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated.

Objective: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7).

Design: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy.

Results: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05).

Conclusion: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.

Publication types

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

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Calorimetry, Indirect
  • Cross-Over Studies
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Fasting
  • Fructose / administration & dosage*
  • Fructose / metabolism
  • Fructose / pharmacokinetics
  • Glucose Clamp Technique
  • Humans
  • Insulin / metabolism*
  • Insulin Resistance
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / physiology
  • Liver / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Muscle, Skeletal / metabolism
  • Sweetening Agents / administration & dosage*
  • Sweetening Agents / metabolism
  • Sweetening Agents / pharmacokinetics
  • Time Factors
  • Triglycerides / blood*


  • Blood Glucose
  • Insulin
  • Sweetening Agents
  • Triglycerides
  • Fructose