Fructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trial

J Hepatol. 2021 Jul;75(1):46-54. doi: 10.1016/j.jhep.2021.02.027. Epub 2021 Mar 6.


Background & aims: Excessive fructose intake is associated with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. We aimed to determine whether fructose elicits specific effects on lipid metabolism independently of excessive caloric intake.

Methods: A total of 94 healthy men were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSBs) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80 g/day) in addition to their usual diet or SSB abstinence (control group) for 7 weeks. De novo fatty acid (FA) and triglyceride synthesis, lipolysis and plasma free FA (FFA) oxidation were assessed by tracer methodology.

Results: Daily intake of beverages sweetened with free fructose and fructose combined with glucose (sucrose) led to a 2-fold increase in basal hepatic fractional secretion rates (FSR) compared to control (median FSR %/day: sucrose 20.8 (p = 0.0015); fructose 19.7 (p = 0.013); control 9.1). Conversely, the same amounts of glucose did not change FSR (median of FSR %/day 11.0 (n.s.)). Fructose intake did not change basal secretion of newly synthesized VLDL-triglyceride, nor did it alter rates of peripheral lipolysis, nor total FA and plasma FFA oxidation. Total energy intake was similar across groups.

Conclusions: Regular consumption of both fructose- and sucrose-sweetened beverages in moderate doses - associated with stable caloric intake - increases hepatic FA synthesis even in a basal state; this effect is not observed after glucose consumption. These findings provide evidence of an adaptative response to regular fructose exposure in the liver.

Lay summary: This study investigated the metabolic effects of daily sugar-sweetened beverage consumption for several weeks in healthy lean men. It revealed that beverages sweetened with the sugars fructose and sucrose (glucose and fructose combined), but not glucose, increase the ability of the liver to produce lipids. This change may pave the way for further unfavorable effects on metabolic health.

Clinical trial registration number: NCT01733563.

Keywords: carbohydrate; lipid metabolism; liver; stable isotopes; sugar.

Publication types

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

MeSH terms

  • Adult
  • Double-Blind Method
  • Energy Intake
  • Fatty Acids / biosynthesis*
  • Fructose* / administration & dosage
  • Fructose* / adverse effects
  • Fructose* / metabolism
  • Glucose* / administration & dosage
  • Glucose* / metabolism
  • Healthy Volunteers
  • Humans
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / physiology
  • Lipogenesis* / drug effects
  • Lipogenesis* / physiology
  • Lipoproteins, VLDL / biosynthesis*
  • Liver* / drug effects
  • Liver* / metabolism
  • Male
  • Sucrose* / administration & dosage
  • Sucrose* / adverse effects
  • Sucrose* / metabolism
  • Sugar-Sweetened Beverages
  • Sweetening Agents / pharmacology
  • Triglycerides / biosynthesis*


  • Fatty Acids
  • Lipoproteins, VLDL
  • Sweetening Agents
  • Triglycerides
  • very low density lipoprotein triglyceride
  • Fructose
  • Sucrose
  • Glucose

Associated data