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

Nynke Simons, Pandichelvam Veeraiah, Pomme I.H.G. Simons, Nicolaas C. Schaper, Eline Kooi, Vera B. Schrauwen-Hinderling, Edith J.M. Feskens, Liesbeth van der Ploeg, Mathias D.G. Van den Eynde, Casper G. Schalkwijk, Coen D.A. Stehouwer, Martijn C.G.J. Brouwers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)


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 (<7.5 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. IHL 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 μmol/d; 95% CI: -91.2, -10.7 μmol/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.This trial was registered at clinicaltrials.gov as NCT03067428.

Original languageEnglish
Pages (from-to)391-400
Number of pages10
JournalThe American journal of clinical nutrition
Issue number2
Publication statusPublished - 2 Feb 2021


  • dietary intervention
  • fructose
  • glucose metabolism
  • hepatic steatosis
  • intrahepatic lipid
  • nonalcoholic fatty liver disease
  • nutrition
  • randomized controlled trial


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