Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men

A randomized controlled trial

  1. Kaspar Berneis, MD1,6
  1. 1Division of Endocrinology, Diabetes, and Clinical Nutrition, University Hospital Zurich, Zurich, Switzerland
  2. 2Human Nutrition Laboratory, Institute of Food, Nutrition and Health, Eidgenössische Technische Hochschule (ETH) Zurich, Zurich, Switzerland
  3. 3Competence Center for Systems Physiology and Metabolic Diseases, Zurich, Switzerland
  4. 4Division of Endocrinology and Diabetes, Kantonsspital St. Gallen, St. Gallen, Switzerland
  5. 5Faculty of Biology and Medicine, Department of Physiology, University of Lausanne, Lausanne, Switzerland
  6. 6Zurich Center for Integrative Human Physiology, Zurich, Switzerland
  1. Corresponding author: Kaspar Berneis, kaspar.berneis{at}
  1. I.A. and M.H. contributed equally to this article.


OBJECTIVE Adverse effects of hypercaloric, high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly. The implications of fructose in amounts close to usual daily consumption, however, have not been well studied. This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism.

RESEARCH DESIGN AND METHODS Nine healthy, normal-weight male volunteers (aged 21–25 years) were studied in this double-blind, randomized, cross-over trial. All subjects consumed four different sweetened beverages (600 mL/day) for 3 weeks each: medium fructose (MF) at 40 g/day, and high fructose (HF), high glucose (HG), and high sucrose (HS) each at 80 g/day. Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production. Lipid profile, glucose, and insulin were measured in fasting samples.

RESULTS Hepatic suppression of glucose production during the clamp was significantly lower after HF (59.4 ± 11.0%) than HG (70.3 ± 10.5%, P < 0.05), whereas fasting glucose, insulin, and C-peptide did not differ between the interventions. Compared with HG, LDL cholesterol and total cholesterol were significantly higher after MF, HF, and HS, and free fatty acids were significantly increased after MF, but not after the two other interventions (P < 0.05). Subjects’ energy intake during the interventions did not differ significantly from baseline intake.

CONCLUSIONS This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose.


  • Received March 21, 2012.
  • Accepted July 8, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents

This Article

  1. Diabetes Care vol. 36 no. 1 150-156
  1. Slide Set
  2. All Versions of this Article:
    1. dc12-0540v1
    2. 36/1/150 most recent