Food and Behaviour Research

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

Geidl-Flueck B, Hochuli M, Németh A, Eberl A, Derron N, Köfeler H, Tappy L, Berneis K, Spinas G, Gerber P (2021) Journal of Hepatology 2021 Mar 5;S0168-8278(21)00161-6 doi: 10.1016/j.jhep.2021.02.027 

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Background & aims: Excessive fructose intake associates with increased de novo lipogenesis, blood triglycerides, and hepatic insulin resistance. Whether fructose-specific effects on lipid metabolism in healthy men exist independently from overfeeding needs clarification.

Methods: 94 subjects were studied in this double-blind, randomized trial. They were assigned to daily consumption of sugar-sweetened beverages (SSB) containing moderate amounts of fructose, sucrose (fructose-glucose disaccharide) or glucose (80g/day) in addition to their usual diet or SSB abstinence (control group) for seven weeks. De novo fatty acid (FA) and triglyceride (TAG) 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) increased basal fractional secretion rates (FSR) of newly synthesized FA by the liver 2-fold 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 (ns)). Fructose intake did not change basal secretion of newly synthesized VLDL-TAG. It did neither alter rates of peripheral lipolysis nor total FA and plasma FFA oxidation. Total energy intake was similar across groups with SSB intake and controls.

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, whereas this effect is not observed after consumption of glucose. These findings support the hypothesis of an adaptative response of the liver to regular fructose exposure, i. e. habitual SSB consumption. The study has a trial registration number of NCT01733563 (


The consumption of high-sugar foods and drinks is strongly linked with development of non-alcoholic fatty liver disease, Type 2 diabetes, obesity and many other conditions involving dysfunctional lipid metabolism - including brain-related conditions such as ADHD, autism, mood disorders and dementia.

However, 'correlation is not causation' - and although animal studies have shown that high fructose intakes can increase fat production, randomised controlled trials in humans have been lacking - until now.

This randomised controlled trial provides strong evidence that even moderate amounts of fructose can cause fatty liver (a precursor to Type 2 diabetes, obesity and other metabolic conditions) - as it showed that fat production in the liver of healthy young men was doubled after just 7 weeks of consuming a daily drink sweetened with either fructose or ordinary sugar (which is an equal mix of fructose and glucose). 

No such effects were seen when the drink was sweetened with pure glucose.  And importantly, these negative effects of fructose were independent of total energy intake, because total calorie intake was not increased throughout the study.

The daily dosage of sugars provided was 80g/day - comparable to 0.8 litres of a normal soft drink - so these findings do not reflect abnormal consumption levels.

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