Effects of fructose restriction on liver steatosis (FRUITLESS); a double-blind randomized controlled trial

Background: There is an ongoing debate on whether fructose plays a role in the development of nonalcoholic fatty liver disease. Objectives: The aim of this study was to investigate the effects of fructose restriction on intrahepatic lipid (IHL) content in a double-blind randomized controlled trial using an isocaloric comparator. Methods: Between March 2017 and October 2019, 44 adult overweight individuals with a fatty liver index >= 60 consumed a 6-wk fructose-restricted diet (<75 g/meal and <10 g/d) and were randomly assigned to supplementation with sachets of glucose (= intervention group) or fructose (= control group) 3 times daily. Participants and assessors were blinded to the allocation. IHI. content, assessed by proton magnetic resonance spectroscopy, was the primary outcome and glucose tolerance and serum lipids were the secondary outcomes. All measurements were conducted in Maastricht University Medical Center. Results: Thirty-seven participants completed the study protocol. After 6 wk of fructose restriction, dietary fructose intake and urinary fructose excretion were significantly lower in the intervention group (difference: -57.0 g/d: 95% CI: -77.9. -39.5 g/d; and -38.8 mu mol/d; 95% CI: -91.2, -10.7 mu mol/d, respectively). Although IHL content decreased in both the intervention and control groups (P < 0.001 and P = 0.003, respectively), the change in IHL content was more pronounced in the intervention group (difference: -0.7% point, 95% CI: -2.0, -0.03% point). The changes in glucose tolerance and serum lipids were not significantly different between groups. Conclusions: Six weeks of fructose restriction per se led to a small, but statistically significant, decrease in IHL content in comparison with an isocaloric control group.

Automated summary

This study found that a 6-week fructose-restricted diet led to a decrease in intrahepatic lipid content in patients with fatty liver disease, with a more pronounced effect in the intervention group. However, there were no significant differences in glucose tolerance and serum lipids between the intervention and control groups.